Saturday, May 5, 2012

MOCK GPAt test

GPAT mock test 
1
http://www.mediafire.com/file/2y637j9m5vfl33z/MINOR%201.pdf

2
http://www.mediafire.com/file/6mn90oud0o2hr8u/MINOR%202.pdf

3
http://www.mediafire.com/file/0lkgpj1bl7hg1ha/MINOR%203.pdf
4
http://www.mediafire.com/file/bxfm0bmxvuv4oh4/MINOR%204.pdf
5
http://www.mediafire.com/file/ealqxb534vxz8fi/MINOR%205.pdf
6
http://www.mediafire.com/file/35ytmb45zunz2t7/MINOR%207.pdf
7
http://www.mediafire.com/file/smkxf7syk17ofza/MINOR%208.pdf
8
http://www.mediafire.com/file/35ytmb45zunz2t7/MINOR%207.pdf

9
http://www.mediafire.com/file/rtlb9h2gf7up2rh/MINOR%209.pdf
10

http://www.mediafire.com/file/vghlrlasgdmaj6h/MINOR%2010.pdf
11
http://www.mediafire.com/file/z99sxp6146b2fuy/MINOR%2011.pdf
12 for Pharmaceutics
http://www.mediafire.com/file/a61gqou7jtz61p0/MINOR%2013%20%20%20P%27ceutics.pdf

13 for Pharmacology
http://www.mediafire.com/file/hbb28x098rxs9h8/MINOR%2015%20P%27cology.pdf

14 for Pharmacognosy

http://www.mediafire.com/file/y7pd8no3xdv3bdp/MINOR%2014%20P%27cognosy.pdf

15
http://www.mediafire.com/file/pb0a2btlz8r1thg/GRAND%20TEST.pdf

Sunday, September 11, 2011

SPX-106T Treatment Yields Significant Reductions in Serum VLDL and LDL Cholesterol in Mice

SPX-106T Treatment Yields Significant Reductions in Serum VLDL and LDL Cholesterol in Mice

 

Spherix Incorporated (NASDAQ: SPEX) – an innovator in biotechnology for therapy in diabetes, metabolic syndrome and atherosclerosis, and providers of technical and regulatory consulting services to food, supplement, biotechnology and pharmaceutical companies – today announced that its drug candidate, SPX-106, achieved statistically significant reductions in VLDL and LDL cholesterol when administered in combination with Dtagatose (SPX-106T) for nine weeks to genetically engineered mice prone to dyslipidemia.  The aortas of these mice also showed reductions in the extent of atherosclerotic lesions as measured by lesion area in response to treatment.  These lipoprotein analysis and lesion measurement results represent the final data from the study whose earlier triglycerides outcome was first announced on June 2, 2011.

Treatment of animals using a range of low doses of SPX-106T twice-daily significantly reduced VLDL by 35% (from 127 mg/dl to 82 mg/dl) and LDL by 18% (from 141 to 116 mg/dl) (p=0.05).  Importantly, the same therapy also reduced atherosclerotic lesion area in the aortic arch to less than one-half the value of the untreated group (graphic available at http://www.spherix.com/pdf/press/PRgraphic9-12-11.pdf).  The aortic arch is generally the region where vessel disease first develops.  In longer studies and in models in which high serum triglycerides fully develops, disease spreads in the vessel from the aortic arch to include the thoracic aorta.  The study was not powered for an atherosclerosis endpoint and the aortas were obtained for post hoc analysis when the effectiveness of SPX-106T in lowering triglycerides and cholesterol became apparent.  

Earlier this year Spherix initiated the preclinical development of SPX-106T as a treatment for hypertriglyceridemia in one arm of a study designed to evaluate both D-tagatose alone and the combination.  The first studies designed specifically to test SPX-106T are nearing completion and results will be announced this fall. The Company plans to start an initial human efficacy study in the first quarter of 2012.  Rapid progression to the clinic is made possible by the experienced team in place at the Company.  

"Having just successfully completed two global clinical trials for a diabetes indication, Spherix has the personnel to design and execute new dyslipidemia trials much faster than other companies of a similar size," notes Dr. Claire Kruger, Chief Executive Officer of Spherix. "The preclinical pipeline of our Biospherics subsidiary can be advanced to the clinical stage rapidly because the Company is able to successfully execute multiple studies simultaneously."

About Spherix

Spherix Incorporated was launched in 1967 as a scientific research company under the name Biospherics Research.  The Company now leverages its scientific and technical expertise and experience through its two subsidiaries – Biospherics Incorporated and Spherix Consulting, Inc.  Biospherics is dedicated to developing and licensing/marketing proprietary therapeutic products for treatment of diabetes, metabolic syndrome and atherosclerosis.  Biospherics is actively seeking a pharmaceutical partner to continue the development of its Phase 3 compound for the treatment of diabetes, D-tagatose, while exploring new drugs and combinations for treatment of high triglycerides, a risk factor for atherosclerosis, myocardial infarction and stroke.  Spherix's Consulting subsidiary provides scientific and strategic support for suppliers, manufacturers, distributors and retailers of conventional foods, biotechnology-derived foods, medical foods, infant formulas, food ingredients, dietary supplements, food contact substances, pharmaceuticals, medical devices, consumer products and industrial chemicals and pesticides.  For more information, please visit www.spherix.com.

Forward-Looking Statements

This release contains forward-looking statements which are made pursuant to provisions of Section 21E of the Securities Exchange Act of 1934. Investors are cautioned that such statements in this release, including statements relating to planned clinical study design, regulatory and business strategies, plans and objectives of management and growth opportunities for existing or proposed products, constitute forward-looking statements which involve risks and uncertainties that could cause actual results to differ materially from those anticipated by the forward-looking statements. The risks and uncertainties include, without limitation, risks that product candidates may fail in the clinic or may not be successfully marketed or manufactured, we may lack financial resources to complete development of D-tagatose, the FDA may interpret the results of studies differently than us, competing products may be more successful, demand for new pharmaceutical products may decrease, the biopharmaceutical industry may experience negative market trends, our continuing efforts to develop D-tagatose may be unsuccessful, our common stock could be delisted from the Nasdaq Capital Market, and other risks and challenges detailed in our filings with the U.S. Securities and Exchange Commission. Readers are cautioned not to place undue reliance on any forward-looking statements which speak only as of the date of this release. We undertake no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this release or to reflect the occurrence of unanticipated events.

SOURCE Spherix Incorporated

Web Site: http://www.spherix.co

Sunday, September 4, 2011

P38 alpha MAP Kinase inhibition: possible therapeutic target for depression

P38 alpha MAP Kinase inhibition: possible therapeutic target for depressionPreclinical Study: A research team from St. Louis and Seattle reports in the Aug. 11 issue of the journal Neuronthat in mice exposed to stress, a protein called p38α mitogen-activated protein kinase (MAPK) influences the animal's behavior, contributing to depression-like symptoms and risk for addiction. The researchers demonstrate that p38α MAPK protein is activated by kappa-opioid receptors on neurons to regulate serotonin, a key neurotransmitter that helps regulate mood. When exposed to stress, the brain releases hormones that specifically interact with kappa-opioid receptors on neurons. Those receptors, in turn, activate p38α MAPK, which then interacts with the serotonin transporter in the cells to reduce the amount of available serotonin and triggering depression-like behaviors as well as drug-seeking behavior in the mice. http://www.cell.com/neuron/abstract/S0896-6273(11)00515-0

How Fatty Diets Cause Diabetes

How Fatty Diets Cause Diabetes Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study led by Jamey D. Marth, Ph.D., director of the Center for Nanomedicine, a collaboration between the University of California, Santa Barbara and Sanford-Burnham Medical Research Institute (Sanford-Burnham), has revealed a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes. These findings were published online August 14 in Nature Medicine. In studies spanning mice and humans, Dr. Marth's team discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes. "We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes," said Dr. Marth."The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility." In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy. In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors -- proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren't working properly, GnT-4a's function is greatly diminished. So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals' beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity. "Now that we know more fully how states of over-nutrition can lead to type 2 diabetes, we can see more clearly how to intervene," Dr. Marth said. He and his colleagues are now considering various methods to augment beta cell GnT-4a enzyme activity in humans, as a means to prevent and possibly cure type 2 diabetes. "The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment," Dr. Marth continued. "This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function." In the United States, more than 24 million children and adults -- nearly eight percent of the population -- have diabetes. In adults, type 2 diabetes accounts for about 90 to 95 percent of all diagnosed cases of diabetes. This study was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Co-authors of this study include Kazuaki Ohtsubo at Sanford-Burnham and Mark Z. Chen and Jerrold M. Olefsky from the University of California, San Diego. Source: http://www.sciencedaily.com/releases/2011/08/110814141432.htm Journal Reference: Kazuaki Ohtsubo, Mark Z Chen, Jerrold M Olefsky, Jamey D Marth. Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport. Nature Medicine, 2011; DOI: 10.1038/nm.2414

Wednesday, August 31, 2011

Possible Trigger Point of Epileptic Seizures Identified

Possible Trigger Point of Epileptic Seizures Identified

Researchers at the Stanford University School of Medicine have identified a brain-circuit defect that triggers absence seizures, the most common form of childhood epilepsy.

 

In a study to be published online Aug. 21 in Nature Neuroscience, the investigators showed for the first time how defective signaling between two key brain areas -- the cerebral cortex and the thalamus -- can produce, in experimental mice, both the intermittent, brief loss of consciousness and the roughly three-times-per-second brain oscillations that characterize absence seizures in children. Young patients may spontaneously experience these seizures up to hundreds of times per day, under quite ordinary circumstances.

The new findings may lead to a better understanding of how ordinary, waking, sensory experiences can ignite seizures, said John Huguenard, PhD, the study's senior author.

Epilepsy, a pattern of recurrent seizures, will affect about one in 26 people over their lifetime. Absence, or petit-mal, seizures -- the form that epilepsy usually takes among children ages 6-15 -- feature a sudden loss of consciousness lasting 15 seconds or less. These seizures can be so subtle that they aren't noticed, or are mistaken for lack of attention. The patient remains still for several seconds, as if frozen in place. Usually, a person who experiences an absence seizure has no memory of the episode.

"It's like pushing a pause button," said Huguenard, professor of neurology and neurological sciences and of molecular and cellular physiology.

Inside the brain, however, things more resemble an electrical storm than a freeze-frame.

The brain is, in essence, a complicated electrochemical calculating machine employing circuits that process information and share it with other, often-remote circuits, resulting in networks of sometimes staggering complexity. A nerve cell can be thought of as a long, branching wire that can transmit electrical signals along its length and then relay these signals to up to thousands of other nerve cells by secreting specialized chemicals at points of contact with other "wires." Depending on the nature of the signaling interaction, the result can be either excitatory (increasing the likelihood that the next nerve cell in the relay will fire its own electrical impulse) or inhibitory (decreasing that likelihood).

During an absence seizure, the brain's electrical signals spontaneously coalesce into rhythmic oscillations, beginning in the neighborhood of two important brain areas, the cortex and the thalamus. Exactly where or how this pattern is initiated has been a source of controversy, said the study's lead author, Jeanne Paz, PhD, a postdoctoral researcher in Huguenard's lab.

"In order to develop better therapies, it is important to understand where and how the oscillations originate," Paz said.

The cortex and thalamus share an intimate relationship. The cortex, like a busy executive, assesses sensory information, draws conclusions, makes decisions and directs action.

To keep from being constantly bombarded by distracting sensory information from other parts of the body and from the outside world, the cortex flags its activity level by sending a steady stream of signals down to the thalamus, where nearly all sensory signals related to the outside world are processed for the last time before heading up to the cortex. In turn, the thalamus acts like an executive assistant, sifting through sensory inputs from the eyes, ears and skin, and translating their insistent patter into messages relayed up to the cortex. The thalamus carefully manages those messages in response to signals from the cortex.

These upward- and downward-bound signals are conveyed through two separate nerve tracts that each stimulate activity in the other tract. In a vacuum, this would soon lead to out-of-control mutual excitement, similar to a microphone being placed too close to a P.A. speaker. But there is a third component to the circuit: an inhibitory nerve tract that brain scientists refer to as the nRT. This tract monitors signals from both of the other two, and responds by damping activity. The overall result is a stable, self-modulating system that reliably delivers precise packets of relevant sensory information but neither veers into a chaotic state nor completely shuts itself down.

In bioengineered mice that the Stanford team studied with Wayne Frankel, PhD, of the Jackson Laboratory in Bar Harbor, Maine, this circuit is broken because the GluA4 receptor, a protein component of cells critical to the stimulation of nRT cells, is missing. Notably, these mice are prone to intermittent absence seizures. The researchers aimed to find out why, by separately studying the mouse's key corticothalamic-circuit components. Using a technique called optogenetics, they were able to selectively switch each of the two stimulatory tracts' signal transmissions on or off at will.

The researchers observed that, as expected, signals from one of the two tracts failed to excite the receptor-deficient mice's inhibitory nRT cells. Oddly, though, signals from the other tract continued to get through to the nRT tract just fine -- "a paradoxical and totally surprising result," said Huguenard.

This leaves nRT receiving signals from one tract, but not the other, which upsets the equilibrium usually maintained by the circuit. As a result, one of its components -- the thalamocortical tract -- is thrown into overdrive. Its constituent nerve cells begin firing en masse, rather than faithfully obeying the carefully orchestrated signals from the cortex. This in turn activates the nRT to an extraordinary degree, because its contact with the thalamocortical tract is not affected in these mice.

Huguenard estimates that, typically, only a very small percentage of nRT cells are firing at a given time. In the face of over-amped signaling from the thalamocortical tract, however, the fraction of excited nRT nerve cells rose much higher, perhaps as much as 50 percent -- enough to effectively silence all signaling from the thalamus to the cortex -- a key first step in a seizure.

But the shutdown was transitory. A property of thalamic cells (like other nerve cells) is that when they've been inhibited they tend to overreact and respond even more strongly than if they had been left alone. After a burst of nRT firing, this tract's overall inhibition of the thalamocortical tract all but halted activity there for about one-third of a second. Like boisterous schoolchildren who can shut up only until the librarian leaves the room, the thalamocortical cells resumed shouting in unison as soon as the inhibition stopped, and a strong volley of signaling activity headed for the cortex. Then the nRT's inhibitory signaling recommenced, and the stream of signals from the thalamus to the cortex ceased once again.

This three-Hertz cycle of oscillations consisting of alternating quiet and exuberant periods repeated over the course of 10 or 15 seconds was the electrophysiology of a seizure.

Whether the specific nRT defect in the bioengineered mice is important in human absence seizures is not yet known, Huguenard cautioned. Most individuals who suffer from these seizures appear to have "normal" nerve cells (individually indistinguishable from those of non-epileptics) and normally formed circuits as well. But now his group has a model experimental system with which they can try to determine why ordinary experiences can trigger these seizures in everyday life. Behavioral experiments are under way in his lab to see what kinds of common sensory exposures can trip off a similar circuit malfunction in normal mice. The resulting observations may someday help patients control their own exposures to minimize seizures, Huguenard said.

Monday, August 15, 2011

Anticholinergics linked to cognitive impairment, increased risk of death

Anticholinergic medications, which are used for a variety of indications including incontinence, may cause cognitive impairment and may increase the risk of death, according to the results of a large study in the UK. A total of 13,004 patients, aged 65 years and older, were evaluated as part of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), a 2-year longitudinal multicenter study investigating health and cognitive function in older adults. At baseline, 9,850 patients (79 percent) reported taking any medication, 5,709 (47 percent) admitted use of medication with possible anticholinergic properties, and 508 (4 percent) said they definitely used anticholinergics. The most frequently used anticholinergic agents were furosemide (N=1,384), dextropropoxyphene (N=955), atenolol (N=992) and nifedipine (N=752), with women more likely to report taking anticholinergic agents than men (7,420 versus 5,003, respectively). [J Am Geriatr Soc 2011 Jun 24. doi: 10.1111/j.1532-5415.2011.03491.x.] At follow-up, the researchers found that patients taking medications with definite anticholinergic effects had a significantly greater 0.33-point decline in their Mini-Mental State Examination (MMSE) score compared to patients not taking anticholinergics (P=0.03). Of particular concern, patients taking definite anticholinergics and possible anticholinergics had a significantly higher mortality rate than patients not using anticholinergics (both P<0.001). “Our findings make it clear that clinicians need to review the cumulative anticholinergic burden in people presenting with cognitive impairment to determine if the drugs are causing decline in mental status,” said Dr. Malaz Boustani, co-author of the study and associate professor at the Indiana University School of Medicine in Indianapolis, Indiana, US. “Physicians should review with older patients all the over-the-counter and prescription drugs they are taking to determine exposure.” “We found that medications with definite anticholinergic effects are independently associated with a greater risk of cognitive decline and death,” added study author Dr. Chris Fox, a psychiatrist from the University of East Anglia, Norwich, UK. While the results of this study are consistent with those of previous trials, the authors said that further research would be needed to determine the effect of of different doses of medicines with anticholinergic activity on mortality. Anticholinergics affect the brain by blocking the central nervous system neurotransmitter acetylcholine. Many drugs with anticholinergic activity are available over-the-counter or by prescription that are taken by adults for a variety of indications, from sleep problems to incontinence.

Monday, July 25, 2011

Agent used to treat tapeworm infection inhibits colon cancer metastasis

Agent used to treat tapeworm infection inhibits colon cancer metastasis Elvira Manzano Niclosamide, an agent which has been around for more than half a century and which is approved for the treatment of intestinal parasite infections from tapeworms, may also be effective against colon cancer metastasis, new research suggests. Scientist Professor Ulrike Stein and colleagues from the Experimental and Clinical Research Center at Charité University Medicine at the Max Delbrück-Center for Molecular Medicine, Berlin, Germany, in collaboration with Professor Robert H. Shoemaker of the National Cancer Institute (NCI) in Frederick, Maryland, US, made the discovery while screening a library of 1,280 compounds for their ability to block the S100A4/metastasin gene, which can trigger colon cancer metastasis. Using high-throughput screening, niclosamide was identified as an S100A4 transcription inhibitor and found to efficiently inhibit the β-catenin-driven expression of the S100A4/metastasin gene both in mice and in cell culture. [J Natl Cancer Inst 2011; 103(12)] S100A4, a calcium binding protein originally identified as metastasin 1 (MTS1), is overexpressed in colon cancer and can initiate metastasis. Overexpression of this gene is also associated with tumor aggressiveness and poor survival in patients. Five years ago, Stein, working with Professor Peter Schlag, of the Charité Comprehensive Cancer Center, Charité University Medicine, in Berlin, Germany, and Professor Walter Birchmeier from MDC, showed how this gene is regulated. They found that the β-catenin gene, when mutant, activates the S100A4 gene, thus triggering colon cancer metastasis. In their latest studies, treatment with niclosamide significantly reduced liver metastasis formation in mice with xenografted intrasplenic tumors compared with controls (P<0.01). More importantly, inhibition of metastasis was still evident 26 days after discontinuation of niclosamide and overall survival was significantly higher in the active treatment group (P=0.001). In vitro, niclosamide-treated colon cancer cells showed reduced S100A4 mRNA and protein levels. The drug also inhibited S100A4-induced migration, invasion, proliferation and colony formation of colon cancers. The researchers said the new anti-metastatic function of niclosamide bears great potential for the treatment and prevention of colon cancer metastasis. Colon cancer is one of the most frequent causes of cancer death worldwide. Despite intensive healthcare programs for early diagnosis, many patients are still diagnosed at an advanced stage of the disease. In Germany alone, about 73,000 new cases of colon cancer are being diagnosed each year, with only about half of these patients cured. In patients with metastatic colon cancer, the 5-year survival rate is only about 10 percent.

Wednesday, July 20, 2011

Heart drugs best taken at bed time, says researcher

Medications for heart patients may do a better job if they are taken at night, just before bed time, according to a researcher in Canada. “Heart drugs are often given to patients in the morning for convenience, without considering biological rhythms or time-related risks of adverse effects,” said Professor Tami Martino from the department of biomedical sciences at the University of Guelph, Ontario, Canada. However, it is better if such drugs are given at bed time, she added, because they are better able to counter the peaking actions of the renin-angiotensin-aldosterone system (RAAS) which is associated with cardiac remodeling. Martino was the lead author of a study which showed that the short-acting ACE inhibitor captopril improved cardiac function and structure in hypertensive mice when given at sleep time, versus placebo or captopril when given during wake time. [J Am Coll Cardiol 2011;57(20):2020-2028] “The sleep-time benefit of giving the ACE inhibitor correlates with the biological rhythm of this hormone,” she said. “By targeting those hormones when they’re highest during sleep, you’re dropping their levels so they’re not doing so much damage.” In the study, mice were administered intraperitoneal captopril 15 mg/kg or placebo at either murine sleep time or wake time for a period of 8 weeks, starting 1 week after surgery to induce cardiovascular pressure overload by transverse aortic constriction. The results also suggest that physicians might consider using a short-acting version of the drug, said Martino. “Since the drug is most effective during sleep hours, it’s not necessary to have its effects last throughout the entire day. Using a short-acting version of the drug may help to reduce its side effects.” It has long been known that diurnal variations exist for the functioning of the human body, and that biological and physiological rhythms play an important role in health and disease. “RAAS is an important pathway in the pathogenesis of cardiac remodelling and hypertrophy,” said Dr. Tang Hak Chiaw, a consultant with the department of cardiology at the National Heart Centre, Singapore. “By targeting the pathway at the time when it is most active, the authors have successfully shown differences in the treatment outcome in an animal model. This paves the way for clinical studies in human subjects.” However, Chiaw said it would be too premature to advise patients when to take their medication based on this study alone. “In our current practice, clinicians would usually choose a medication that has a longer duration of action to give 24-hour coverage [or] protection if there is an option. Of course, this study [will] generate interest and, as the authors have appropriately concluded, their findings will “provide new opportunities for the effective treatment of cardiovascular disease.” – GT

Excessive bottle feeding can lead to childhood obesity

Children who still drink from bottles at age two are at risk of becoming obese by age five, a new study shows. The American Academy of Pediatric Dentistry recommends weaning children from bottles at 12 to 14 months. Prolonged bottle use, particularly at bed time, can cause tooth decay and bacterial infections like caries. However, 22 percent of 6,750 children involved in a large national US study were still drinking primarily from a bottle or were put to bed with a bottle at 24 months of age. Almost 23 percent of these children were obese (in the 95th percentile for body mass index [BMI]) by age 5.5 years, compared with 16 percent of children who had been weaned from bottles earlier. [J Pediatr. 2011 Apr 27. Epub ahead of print] “Drinking from a bottle beyond infancy is a behavior that could contribute to obesity by encouraging the child to consume excess calories,” commented the study authors, led by Rachel Gooze, a doctoral candidate in public health at Temple University’s Center for Obesity Research and Education in Philadelphia, US. For example, they noted that an average weight (about 12 kg) 2-year-old girl put to bed with an 8-ounce bottle of whole milk gets 12 percent of her daily caloric needs from the bottle. Weight gain would depend on how much excess these calories represent. In general, children should begin eating a variety of solid foods at about 6 months in addition to about 16 ounces of milk and no more than about 4 ounces of juice, plus more water. Prolonged bottle use is often a comfort issue for children and parents. Smaller, cross-sectional studies have suggested an association between prolonged bottle use, particularly at bed time, and weight gain but this is the first prospective study of size to do so. This latest study was limited by confounders such as physical activity and diet, where over-fed children may have had a higher caloric intake of nutrition-poor foods like sugary drinks as well as being less likely to have breastfed. The researchers did control for confounders including socioeconomic status, maternal obesity, breast feeding, age at introduction of solid foods and weight at birth and at 9 months. Under-reporting by parents of prolonged bottle use among heavier children may also have falsely decreased the association with obesity. It is unclear whether the association holds beyond 5.5 years. “A multilevel obesity prevention strategy is considered optimal because it alters children’s social and physical environments in multiple settings, such as the home, child care, school, and neighborhood,” the researchers said, and noted that discontinuing bottle use after one year will not be harmful and may help prevent obesity.

Friday, June 3, 2011

Lupin inks strategic deal with NeuClone for cell line technology

 Lupin has entered into a strategic licensing agreement with Sydney based private specialty life science company NeuClone Pty Ltd for their cell line technology. Under the terms of the agreement, NeuClone will provide an exclusive proprietary mammalian CHO cell line which will express a specific recombinant protein of interest in oncology to its partner.

The agreement will also entail the Lupin Biological Research Programme scientific research staff working with NeuClone teams at their facility as a part of the overall technology transfer arrangements as specified within the agreement. NeuClone is an Australian biotech company specializing in cell line engineering for the biopharmaceutical and biomanufacturing industries. It has developed technology in recombinant protein production.

Dr Cyrus Karkaria, president, Lupin and Head of the Lupin Biological Research Programme said, “the multi-billion dollar opportunity with blockbuster biologics going off patent in the next 5-8 years is something that Lupin is pursuing aggressively. This exclusive licensing arrangement with NeuClone is a part of that strategy and would enable us to capitalize on cutting edge technology to address the biologicals market. This agreement and such similar agreements, coupled with our own pipeline will go a long way in helping us address the impending opportunity and develop a substantial differentiated biological pipeline.”

Dr Noelle Sunstrom, CEO of NeuClone, said, “This is an exciting time for NeuClone and our stakeholders as our investment in mammalian CHO cell lines is commercialized. In particular, we are enthusiastic about further developing the relationship with Lupin, an important global generic manufacturer.”

Source: Pharmabiz

US FDA approves Solesta to treat patients with life-altering fecal incontinence

 Oceana Therapeutics, a global company focused on acquiring, developing and commercializing best-in-class specialty therapeutics, announced that the US Food and Drug Administration (FDA) has approved Solesta as a treatment for fecal (bowel) incontinence in adult patients who have failed conservative therapy such as dietary control.

“This is a pivotal development, one that advances Oceana Therapeutics to an exciting new growth stage,” said John T Spitznagel, chairman & CEO, Oceana. “Moreover, Solesta epitomizes our corporate mission to commercialize specialty therapeutics for unmet medical needs and to achieve optimal outcomes and enhanced patient quality of life” he added.

David S Tierney, president & COO, Oceana said “Solesta was developed in collaboration with Q-Med AB* as a minimally invasive injectable gel that can be administered, relatively quickly, in an outpatient setting without the need for anaesthesia. This is a significant new treatment option for the many underserved patients who fail conservative therapy and face a life of potential social humiliation and the possibility of severe invasive treatment such as surgery.”

“I also want to commend everyone involved in the speedy responses to the items raised about a month ago in the FDA’s approvable letter for Solesta,” said Tierney. “The turnaround time between the FDA’s approvable letter and today’s announced marketing approval of Solesta has been, in our view, remarkably fast.”

Oceana intends to focus Solesta marketing and medical educational support on colorectal surgeons, specialists in treating bowel incontinence. The company is also moving expeditiously to put in place marketing materials, build product inventory, and be prepared to ship and launch Solesta during the second half of 2011. “The sooner we get Solesta into the hands of the physicians, the sooner it will be available to patients who can benefit from the product,” said Tierney. “So, we intend to push hard for a 3rd quarter US launch, although we realize that is an aggressive target.”

Solesta is a biocompatible tissue bulking agent, consisting of dextranomer microspheres and stabilized sodium hyaluronate. Solesta has been developed as a minimally invasive treatment for fecal incontinence. It is the only injectable gel to be administered in an outpatient setting without the need for anaesthesia. Solesta is injected in the deep submucosal layer in the proximal part of the anal canal. While the exact mechanism of action has not been identified, it is hypothesized that the Solesta injections may narrow the anal canal and allowing for better sphincter control.

The Solesta PMA was submitted to the FDA in April 2010 for the treatment of fecal incontinence in adult patients who have failed conservative therapy (i.e., diet, fibre therapy, anti-motility medications). The PMA was reviewed by the FDA’s Gastroenterology and Urology Devices Advisory Panel which met on December 2, 2010 and which voted that Solesta was safe and effective, and that its benefits outweighed its risks.

The main body of clinical evidence in the Solesta PMA submission involved a multi-centre, prospective, randomized, Sham (placebo) controlled study of the product’s effectiveness and safety. The study included 206 patients (136 Solesta, 70 Sham) and consisted of a 6-month double-blinded phase followed by an open label phase in which patients originally randomized to Sham treatment were offered Solesta. The primary efficacy objective of the study required: demonstrating a statistically significant Solesta effect after 6 months of treatment; meeting a pre-defined threshold for clinical significance; and showing durability of the Solesta benefit up to 12 months after treatment. All three of these endpoints were met.

Results from this clinical trial of Solesta as a treatment for fecal incontinence were published in The Lancet (March 19, 2011; 377: 997-1003). In general, the authors of the article noted that the treatment not only met its safety and efficacy endpoints, but also was easily administered.

Oceana Therapeutics is committed to commercializing best-in-class therapeutics to address unmet and under-satisfied medical needs with a focus on colorectal, gastroenterology and urological diseases.

Source: Pharmabiz

Himalaya partners with Karnataka govt to rehabilitate prisoners by roping them into herbal cultivation

 Himalaya Herbal Healthcare signed an agreement with the Department of Prison Rehabilitation, Government of Karnataka, to create employment opportunities for prisoners, with the objective of rehabilitating them.

According to the agreement, the prisoners will cultivate medicinal herbs for Himalaya. This will help in skill-building and employment generation. The program will target prisoners charged with minor offences, who have shown good behaviour and a desire to rebuild their lives.

In phase I of the project, the herb cultivation will be undertaken at the Open Air Prison at Avathi village in Devanhalli Taluk. Initially, cultivation will be carried out on a small plot of land, approximately one to two acres. While the open air prison has a large tract of land available for cultivation, the first phase of the project will start small, in order to strengthen logistics.

Inmates of the open air prison will participate in the herb cultivation project, earning a regular monthly income and acquiring essential skills. Himalaya will provide seeds and technical assistance along with training to the prisoners. Once the system begins to operate smoothly and efficiently, Himalaya will explore the possibility of scaling up the project and expanding scope to other prisons across the state.

According to Dr Babu, Head – Agrotech Department, The Himalaya Drug Company, said “Society can be very unforgiving to prisoners. We stereotype them as criminals and never really give them a chance to rehabilitate themselves. Himalaya’s corporate social responsibility program focuses on reaching out to underprivileged sections of society through livelihood development. That is why when the Government of Karnataka approached us with this proposal, we were very excited. With the right support and encouragement, some of these prisoners can be effectively rehabilitated. This project will give prisoners an opportunity to earn a decent income and acquire new skills. In a small way, our efforts will help them rebuild their lives by giving them a fair chance.”

Prison reform is essential. Equipping prisoners with basic skills through such initiatives will help them in future employment, build their self-esteem and assist their re-integration into society.

Source: Pharmabiz

Orthocon receives US FDA clearance to market Hemasorb Apply

 Orthocon Inc., a privately-held therapeutic device company, announced that the Food and Drug Administration cleared Hemasorb Apply for clinical use and sale in the United States.

Hemasorb Apply is a proprietary, custom-designed applicator preloaded with Hemasorb Absorbable Bone Haemostat Matrix. The product is provided ready-to-use and enables precise application of Hemasorb to stop bone bleeding during surgical procedures and in treating traumatic injuries. Currently marketed bone haemostat products require surgeons to use their fingers or surgical instruments for application. Unlike bone waxes, Hemasorb is putty-like in consistency, does not require preparation, and is now provided in a syringe-like applicator. Furthermore, Hemasorb is absorbable, biocompatible, and water resistant.

Commenting on the significance of the Hemasorb Apply clearance, John J Pacifico, president and chief executive officer, Orthocon said the following: “This regulatory clearance is an important achievement for Orthocon. There has been very little innovation in the bone haemostat field since bone wax was first introduced in the late 1800s. We believe that the widespread adoption of flowable surgical haemostats has created new opportunities for advanced surgical products that more efficiently and effectively control bone bleeding, and we are confident that Hemasorb Apply will help secure Orthocon’s leadership position in this therapeutic category. Both Hemasorb and Hemasorb Apply are clearly differentiated from wax-like haemostats, and they are changing the way surgeons think about surgical haemostasis.”

Since its initial market introduction in 2010, Hemasorb has been approved for sale at leading hospitals throughout the United States and has been used successfully by hundreds of surgeons. Orthocon is confident Hemasorb Apply will provide surgeons with an innovative and cost effective tool to assist in their management of intra-operative bone bleeding, and the company fully expects Hemasorb to become the standard of care for bone haemostasis.

Control of bleeding from cut bone is a problem in many operative procedures including spine, orthopaedic, craniomaxillofacial, and cardiac surgeries. Excessive bleeding during surgery may impair the surgeon’s view of the operative field, may result in the need for blood transfusions, and may be associated with postoperative complications. Orthocon estimates that over 3.5 million patients undergoing surgeries in the United States, Europe, and Canada each year could benefit from the intra-operative use of Hemasorb.

Orthocon develops, manufactures, markets, and sells implantable products that stop bone bleeding.

Source: Pharmabiz

Thursday, June 2, 2011

FDA approves new treatment for a type of late-stage skin cancer

FDA approves new treatment for a type of late-stage skin cancer Melanoma patients lived longer with treatment The U.S. Food and Drug Administration today approved Yervoy (ipilimumab) to treat patients with late-stage (metastatic) melanoma, the most dangerous type of skin cancer. Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010 and about 8,700 people died from the disease, according to the National Cancer Institute. “Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient’s life,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. "Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment." Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously. Yervoy’s safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed. The study was designed to measure overall survival, the length of time from when this treatment started until a patient's death. The randomly assigned patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone. Those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months. Common side effects that can result from autoimmune reactions associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). Severe to fatal autoimmune reactions were seen in 12.9 percent of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks. Due to the unusual and severe side effects associated with Yervoy, the therapy is being approved with a Risk Evaluation and Mitigation Strategy to inform health care professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy's potential side effects. Yervoy is marketed by New York City-based Bristol-Myers Squibb.

admission: Guru Jambheshwar University of Science & Technology

Institute: Guru Jambheshwar University of Science & Technology Programme: GROUP 1: M.Sc. (Applied Psychiology), M.Sc. (Development communication), M.Sc.(Advertising Management & Public Relations), M.Sc. (Mass Commmunication), P.G. Diploma in Web Advertising & Animation, P.G. Diploma in Tourism PR, P.G. Diploma in Defence Journalism. GROUP 2: M.Sc. (Chemistry), M.Sc. (Physics), M.Sc. (mathematics), M.Sc. (Biotechnology), M.Sc. (Environmental Sciences), M.Sc. (Food Technology), M.Sc. (Industrial Microbiology), P.G. Diploma in Pigment and Paint Technology. OTHER COURSES M.Pharma Programmes M.Pharma (Pharmaceutical Chemistry), M.Pharma (Pharmaceutics) M.Pharma (Pharmocolgy), M.Pharma (Pharmacognosy), M.Tech.(Computer Science & Engineering), M.Tech.(Environmental Science & Engineering), M.Tech.(Electronics & communication Engineering), M.Tech.(Machanical Engineering), M.Tech.(Printing Technology), M.Tech.(Nano Science & Technology), M.Tech.(Optical Engineering), M.Tech.(Computer Science & Engineering), M.Tech.(Food Engineering), M.Tech.(Geo- Informatics). Masters of Physiotherapy M.Pth. (Musculoskeletal Disorders), M.Pth. (Sprots Phisiotherapy), M.Pth.(Neurological Disorders), M.Pth.(Pediatric physiotherapy), Bachelor of physiotherapy. Eligibility: Click here for more details Selection process: For detailed selection process click here How to apply: The candidates are required to apply only on the prescribed Admission Form given in this Prospectus or the downloaded one from the University website (with requisite fees in case of downloaded admission form). Important dates: Availability of prospectus/ Admission form on University website: May 29, 2011 On-the-Counter sale of prospectus: June 03, 2011 Last date for receiving request for issue of University prospectus by post: June 24, 2011 Last date for counter sale of University prospectus and submission of filled in application forms: July 04, 2011 Address: Guru Jambheshwar University of Science & Technology, Hisar - 125001 Haryana (India) Phone: 01662-263139 Website: www.gjust.ac.in http://www.gjust.ac.in/downloads/downloads.htm

Optimer's Clostridium difficile drug

The US Food and Drug Administration has given the green light to Optimer Pharmaceuticals' antibiotic Dificid. Dificid (fidaxomicin) has been approved for the treatment of Clostridium difficile–associated diarrhoea (CDAD), making it the first antibacterial indicated for the disease to be approved by the FDA in nearly 30 years. CDAD rates have steadily risen over the past decade and it is estimated that more than 700,000 cases of the infection occur in the USA each year. The infection is a significant problem for the elderly in hospitals and care homes. Related Links Astellas signs antibiotic deal with Optimer The thumbs-up is based on two Phase III trials involving 564 patients and compared Dificid with vancomycin, a common antibiotic used to treat CDAD. The clinical response was similar in the Dificid group compared with vancomycin in both studies. However, the FDA noted that in some patients with CDAD, symptoms can return and in the Dificid trials, a greater number of patients treated with the Optimer drug had a sustained cure three weeks after treatment ended versus those patients treated with vancomycin. Last month, Optimer signed a two-year co-promotion deal for Dificid with Cubist Pharmaceuticals, which is best-known for Cubicin (daptomycin), approved for the treatment of complicated skin infections and bacteremia caused by MRSA. The latter firm will receive $15 million a year for its services and can earn up to $17.5 million over the two years if certain sales levels are achieved. Optimer plans to hire 100 sales reps to promote Dificid to the 1,100 hospitals that account for 70% of CDAD cases in the USA. Chief executive Pedro Lichtinger said that "the recognition in our label of the Dificid superiority in sustained clinical response will allow the Optimer and Cubist field force to educate the medical community" about the advantage the product offers.

Monday, May 23, 2011

Cancer nanotechnology: current scenario

 Cancer is one of the leading causes of mortality worldwide. Every year, a large number of patients suffering from cancer die. This number is continuously rising with an estimation of about 12 million deaths from cancer by 2030. The current treatment given to cancer patients primarily includes chemotherapy (where anticancer drugs are used to kill the cancer cells) and radiation therapy (where radiations are focused on the infected areas to kill the cancer cells). However, both the therapies are associated with severe toxicities due to their inability to differentiate between cancer cells and normal cells. Hence, to overcome this, many laboratories are trying to develop an arsenal based on nanotechnology to fight against this dreadful disease. In this article, the nanotechnologies used for treating cancer have been discussed briefly.

Why nanotechnology?

Over the past few years, many pharmaceutical companies, institutions and R&D laboratories all over the world are trying to develop nanotechnology based drug delivery systems. Nanotechnology, as defined, is the creation and application of devices, drugs or any materials that are in the size range of 1-100 nm in size. This extremely small size of such appliances offers several advantages in drug delivery while treating diseases like cancer. The major advantage is the ability of such systems to penetrate the biological membranes with ease and become available at the target site. As a result, nanotechnology has found very wide applications in drug delivery systems.

Current cancer nanotechnologies

Nanobiosensors have found to have diagnostic applications in cancer. A biosensor is basically made up of several components including sensitive biological element, a transducer and a detector with the help of which they detect the analyte. Typically when such a device is in nano dimensions, they are termed as nanobiosensors. Many different types of nanobiosensors have been produced which are claimed to be of use in early cancer detection. The cancer specific ligand or antibody present in such sensors selectively captures cancer cells thereby producing signals, which are ultimately detected by the detector. Such devices are projected to be of utmost importance for cancer diagnostics in future.

Liposomes have been used to deliver drugs in various cancer indications. With its help, the concentrations of anticancer agents at the target site have found to increase and thereby better efficacy and bioavailability can be expected from such systems. For instance, many anticancer drugs like Doxorubicin and Docetaxel have been used using liposomes as the drug delivery system. One of the most important advantages of liposomes as a carrier system is that they are made up of lipids which are biocompatible and non toxic to the human body.

Dendrimers are a class of macromolecules, which are repeatedly branched. They have found their applications in many fields including engineering, medicine, nanobiotechnology, to name a few. More than 5000 patents and publications have been reported on this novel class of molecules regarding their synthesis and potential applications. They have been projected to be a potential MRI contrast agent that can be utilised for diagnosis and treatment in cancer therapy. One of the research groups at the University of Michigan have successfully synthesised dendrimer-based MRI contrasting agent, which successfully targeted tumors in animal models.

Nanoparticles, including polymeric nanoparticles and lipid nanoparticles are used in research for their applications in drug delivery for cancer. Many biodegradable polymeric nanoparticles like PLGA (poly lactide co glycolic acid) and PEG (poly ethylene glycol) have been utilised as drug delivery carriers for anticancer agents. Being biodegradable they are non-toxic and can be degraded within the human body to release the drug. With the help of such polymeric nanoparticulate systems, sustained release of drugs have obtained a reduction in the associated toxicities. A large number of anticancer agents like Docetaxel, Doxorubicin, Cisplatin, Doxorubicin have been successfully encapsulated in such carrier systems. In addition, such polymeric nanoparticles have also shown to simultaneously encapsulate two drugs, thereby aiding in dual drug delivery and better efficacy. Such systems also help in better targeting of the drugs at the infected areas, thereby minimising toxicities.

Besides this, many different types of quantum dots, nanoshells, nanocantilevers, nanowires, nanotubes and fullerenes have been synthesised, characterised and researched for their potential applications. Quantum dots-based nanobiosensors have been developed. Nanoshells have also found applications in cancer treatment. Hollow Gold NanoShells (HGNS) have shown to be of use in photothermal therapy wherein such systems, after they reach the infected areas, are irradiated due to which they get heated and kill the cancer cells. Such systems have shown great promise for future cancer treatments.

Currently, many scientists are also trying to combine and integrate different systems in one system. For instance, many scholars at Nanobios laboratory at Indian Institute of Technology Bombay, are trying to encapsulate one or two anticancer drugs in a polymeric system to which gold nanoshells are attached. Such systems may be given intravenously directly to the infected areas. After reaching the target site, they can be irradiated as a result of which gold nanoshells get heated up and kill the cancer cells. Also due to the heat generated, polymeric particles may get degraded or thermoresponsive polymeric system may release the anticancer agents encapsulated within it. Such systems seem to be a great breakthrough in cancer therapy where radiation therapy and chemotherapy is combined into one system. Such systems are also projected to reduce the side effects and associated toxicities due to the conventional radiation therapy or chemotherapy.

To conclude, we can say that current cancer nanotechnologies have shown great promise for their practical applications in the diagnosis and treatment of cancer. However, plenty of research is still required especially focusing upon their toxicities and efficacy.

Source: ExpressPharma

Venus Remedies completes phase I & II trials of cancer molecule

 

Venus Remedies recently announced that it has successfully completed phase I and II clinical trials for VRP1620, Tumatrek, which could become a cost effective diagnostic tool for cancer. The clinical study has shown excellent results in detection of breast cancer. With this molecule, detection of breast cancer would be possible with a simple X-ray using dye and the sensitivity of other detection devices such as coloured doppler, PET would be increased several times.

Dr Manu Chaudhary, Research Director, Venus Remedies said, “VRP 1620 (Tumatrek) is a unique and cost effective diagnostic tool for cancer which can also detect malignancy even through X-ray. It can detect cancer at a lower cost and at the primary stage itself.” Detection of cancer in the early stage can increase the cure rate and scientists believe that after phase III trials of this product VRP-1620 may also help in locating proliferation of cancer sites.

For the past few years, a team of scientists from Venus Medicines Research Center (VMRC), the R&D wing of the company, were working on a novel peptide VRP 1620, which is a highly selective ETB receptor agonist and is involved in selective vasodilation in solid tumours. “Phase III will be completed this year and the product will be ready for market launch in early 2012,” Chaudhary added.

Venus Remedies has completed and submitted the report of phase I and II study on breast cancer patients for VRP 1620 after due permission from the IND committee and DCGI, Government of India. Phase I was conducted at Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh to find the maximum tolerable dose. Later phase II clinical study was conducted at multiple institutions throughout India including PGIMER, Chandigarh and Central India Cancer Research Institute, Nagpur, Maharashtra.

This clinical study documented the pharmacokinetic profile and appropriate dose range for the drug. It also described the efficacy for its use as a diagnostic agent for breast cancer. The efficacy was gauged by observing increase in diameter and the corresponding change in resistive index of tumour vessel. An increase of 17.31 per cent in tumour vessel diameter was observed compared to baseline 12-15 minutes after drug administration of VRP-1620 at dose levels 0.8 µg / kg body weight. Corresponding to this increase in tumour vessel diameter there was a decrease in RI (resistive index) 7.15 per cent. These changes indicate an increase in tumour blood perfusion causing the contrast media to deeply penetrate, creating a better tumour silhouette.

Tolerability of VRP 1620 was also assessed by the investigators and subjects at the end of study treatment period, which showed that the product is well tolerated.

Cancer prevalence in India is estimated to be around 2.5 million, with over 8,00,000 new cases and 5,50,000 deaths occurring each year due to this disease. More than 70 per cent of the cases report for diagnostic and treatment services in the advanced stages of the disease, which has lead to a poor survival and high mortality rate. The product has huge potential in urban and semi urban belts where advanced technologies of cancer detection are not available. This technology will provide a cutting edge in timely detection of cancer and has tremendous need especially in under developed and developing countries.

The global cancer market was worth $56.7 billion in 2007, growing at 16.8 per cent over 2006, and is forecast to reach a value of $76.9 bn by 2013 representing a CAGR of 5.1per cent (2007-13). Oncology is one of the leading therapeutic categories in the global pharma market. The Indian oncology market is estimated to be about Rs 7,000 to 8,000 million, growing at a CAGR of more than 30 per cent in the last three years. The economic toll from cancer, estimated to be $895 billion, is nearly 20 per cent higher than heart disease, the second leading cause of economic loss ($753 billion).

 

Source: ExpressPharma

Suven granted seven product patents

 Suven Life Sciences announced the grant of seven product patents (two from Canada, three from India, one each from Eurasia and Japan) corresponding to the New Chemical Entities (NCEs) for the treatment of disorders associated with neurodegenerative diseases. These patents are valid through 2023, 2024 and 2025.

The granted claims of the patents include the class of selective 5-HT compounds discovered by Suven and are being developed as therapeutic agents and are useful in the treatment of cognitive impairment associated with neurodegenerative disorders like Alzheimer’s disease, attention deficient hyperactivity disorder (ADHD), Huntington’s disease, Parkinson’s syndrome and schizophrenia.

With these new patents, Suven has a total of five granted patents from Canada, 13 granted patents from India, nine granted patents from Eurasia and four granted from Japan for NCEs. These granted patents are exclusive intellectual property of Suven and are achieved through the internal discovery research efforts. Products out of these inventions may be out-licensed at various phases of clinical development like at phase-I or phase-II.

"We are very pleased by the grant of these patents to Suven for our pipeline of molecules in CNS arena that are being developed for cognitive disorders which has an estimated $30 billion market potential globally,” said Venkat Jasti, Chief Exceutive Officer, Suven.

Source: ExpressPharma

ASTHMA To Claim Younger Victims

 Like in many other segments, the revenue growth in seven major markets (the US, UK, Italy, Spain, Germany, France and Japan) is expected to slow down from 2010 to 2012 in the respiratory/asthma therapeutic segment. This decline could be attributed to expiry of patents of leading brands and resultant price erosion. In the current scenario countries like India, China etc, which have a strong generic presence, apart from the need to provide medical aid to a growing patient population, also have a good business opportunity.

Decision Resources and GlobalData had estimated that the global asthma drug market was $12.4 billion in 2009, registering an expected compound annual growth rate (CAGR) of 1.5 per cent which would grow to $14 billion by 2017. It is also reported that India's asthma drug market, which was estimated to be worth $246 million in 2009 is likely to grow at an annual growth rate of approximately 10 per cent to reach $403 million by 2014. This is close to some European Union countries in terms of value. Rahul Sehgal, President, Nestor Pharmaceuticals remarks on its market potential, “I would personally feel that the domestic pharma companies are likely to emerge as more competitive and aggressive players in the coming time. “

Shakti Chakraborty, President – India Region Formulations, Lupin also agrees with this estimate, saying, “We have seen no dearth of opportunities or lack on the part of domestic pharma companies to drive growth; rather we have seen a steady increase in our volumes and market share over the years.

Hitesh Gajaria, Executive Director, KPMG India says, “Domestic companies have a very strong presence in India’s asthma therapy market, much more than multinational companies.“ Some of the leading domestic players in this therapeutic area are Dr Reddy’s (DRL), Lupin and Cipla. A few of the MNCs active in the domain are GSK, AstraZeneca and Merck.

The therapy for asthma varies from corticosteroids to beta-agonists, and due to the availability of multiple drugs that act through multiple modes of action, there is an increase in scope for different players. There are more than 120 companies in the Asthma market with approximately 50 branded drugs, Gajaria adds.

Chakraborty explains, “The Indian Council of Medical Research (ICMR) reported that 13 million people in India over the age of 15 suffer from asthma, or around two per cent of this total age group. Nearly seven million are men, and just over six million women. The worst-affected age group is the 15-35-year-olds.

Over the years, the prominent trend emerging in India in respiratory ailments is its increased incidence in children. While asthma and bronchitis were ailments largely restricted to the elderly, over the years, research has shown that an increasing number of children are being affected by this. A lot of this is correlated to demographic changes in Indian cities, like the increase in the number of industries, density of population by migration from rural areas in search of jobs, and increased number of carbon-emitting automobiles on Indian roads, amongst others.

Global scenario

The countries worst affected by asthma are Ireland, the UK, Australia and New Zealand. Sehgal shares global facts and figures. In Australia, one child in six under 16 suffers from this condition. In Western Europe, the number of Asthma cases has doubled in the last decade. In the US the number has risen by 60 per cent since early 1980s. Around 5000 Americans die from asthma each year. Asthma is 26 per cent more prevalent in black than white American children. Around eight per cent of the Swiss population suffer from asthma, compared with just two per cent 25 years ago. There are four million asthmatics in Germany, some three million Japanese are suffering from the condition, of whom seven per cent have severe symptoms and 30 per cent have moderate problems. In India, it is estimated that there are up to 20 million asthmatics, with up to 15 per cent of children aged five to 11 years old having the symptoms. In Brazil, Costa Rica, Panama, Peru and Uruguay the percentage is nearly 30 per cent, whereas in Kenya 20 per cent of children have asthma.

It would be only apt to say that most countries would offer a fair market based on affluence/buying capacity and population value centric sales will be high. Since the resources available to MNCs are large compared to domestic players, it is possible for them to be more aggressive in terms of marketing and endorsing drugs. However, with patents for most drugs expiring and with the increased production of generic versions by domestic players, cheaper alternatives will be preferred so this advantage is no longer as valid as it was a couple of years back..

Highlighting the intense capabilities of Indian pharma players Gajaria says, “In India, domestic players are powerful in their own right. Players like Lupin and Dr Reddy's are money spinners with intensive product portfolios and impressive generic capabilities with the ability to successfully position their products in the market. Fixed-dosed combination (FDC) drugs are the latest in asthma therapy and represent a major opportunity for multinational pharma companies. The use of combination therapy as maintenance treatment will gradually pick up in India where the practice is still to treat asthma on an as-needed basis as opposed to treating it as a chronic disease that requires maintenance-treatment. However, even as this trend of treatment picks up, the competition will only intensify.”

Acute respiratory diseases in India have grown by 33 per cent from 2005-2010, which is a significantly higher rate compared to other communicable diseases. This increase could be curbed by improved access to medical care, a growing drug-treated population and a rising number of higher-income, brand-conscious asthma patients demanding more efficacious agents.

Proper therapy

Indian specialists struggle with patient compliance when treating asthma. The importance of consistent maintenance therapy is paramount because improved disease outcomes are not achieved unless continuous therapy is administered consistently. “The Indian asthma market would benefit from new, more convenient therapies, which would boost patient compliance,” adds Sehgal.

Gajaria remarks, “Asthma requires diligent maintenance therapy, with many multiple dose regimens. The therapy is usually complicated and the schedules are not simple. It is often observed that lack of patient education leads to under dosing and hence ineffective treatment. With a large population of illiterate patients, the specialists struggle to ensure complete dosing and hence effective disease management. Combination fixed dose drug treatment could be a possible answer to this problem, and could ensure in simplifying the treatment regimen thus ensuring more compliance.”

A Ranbaxy spokesperson emphasises, “Ranbaxy is committed to providing patient friendly solutions for the effective management of respiratory disorders. The company offers a wide range of innovative products in the Asthma segment to suit the convenience of patients.”

Chakraborty opines that Indian specialists struggle with patient compliance when treating Asthma. Consistent maintenance therapy is of prime importance because effective therapies are not achieved unless maintenance procedures are administered consistently. The Indian asthma market would benefit from new, more-convenient therapies, which would boost patient compliance.

Lupin has also taken several initiatives involving doctors as well as end customers. Chakraborty justifies, “We have brought in specialists from abroad to educate doctors and also set up asthma awareness camps in rural as well as urban areas around the country. We aim not only to treat existing patients but also to share methods to avoid practices that cause asthma. These camps are set up to raise awareness of asthma in order for people inflicted with this disease to seek the appropriate treatment in a timely manner,to properly screen patients for those who are suffering from asthma through practical and objective methods/measurements,to provide asthma medications which are affordable and can be administered by patients themselves on a daily basis and to track patient progress and outcomes in order to measure the level of success of this project so as to ultimately determine the most effective ways to improve the conditions of patients with asthma in rural India. “

Government support

The Indian Government has taken a few initiatives in the past in this regard, like in November 2009 the Indian Council for Medical Research (ICMR) and the UK Medical Research Council (MRC) jointly hosted a workshop in New Delhi. Experts from India and the UK reviewed the current disease burden in their respective countries. The partnership between ICMR and MRC aimed to combine the strengths of the Indian and UK chronic disease research communities. Gajaria recommends, “The Government should make attempts to ensure educating the public about these lifestyle related diseases; knowledge about the disease is the first step to fighting it. Chronic diseases like diabetes, cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and other respiratory diseases, including asthma, face intense patient non-compliance which stems from lack of education and trust. The Government can collaborate with pharma companies, or with other non profit healthcare organisations to change this situation.”

Sehgal shares a similar view, “Greater advocacy is required to raise global awareness of this growing threat and to help dispel some myths surrounding chronic diseases, including the myth that a chronic disease cannot be prevented and that these diseases only burden high income countries. Tobacco smoke and indoor and outdoor pollution are two major causes of chronic diseases and both are preventable but India has no national programme to tackle the problem.” Adds Chakraborty, “The government should focus on improving sanitation standards and set up more powerful pollution control initiatives to begin with. Educational camps, seminars should be conducted and awareness material about the disease should be given at a rural as well as district level.”

Chakraborty summarises, “We are confident of maintaining our existing pace of growth and going forward, we will introduce more and more patient-friendly and high-quality drugs and delivery mechanisms to counter asthma. We expect to sustain our growth and increase our market share from the existing 18 per cent even further in the future.”

Source: Express pharma

Sunday, May 22, 2011

GNDU-Guidelines for application and admission for M.Pharm-B.Pharm 2011-2012

Guru Nanak Dev University, Amritsar (Punjab) http://www.gnduadmissions.org GNDU-Guidelines for application and admission for M.Pharm-B.Pharm 2011-2012 Course Details : B. Pharmacy Total Seats-30 Eligibility Secondary School Examination of Punjab School Education Board (10+2) system with a minimum of 50% marks in Chemistry, Physics and Biology in aggregate or any other examination with of 50% marks in Chemistry, Physics and Biology in aggregate recognized as equivalent to it. Course Details : M. Pharmacy Total Seats-30 Eligibility B.Pharmacy degree examination of Guru Nanak Dev University or any other recognized University/Institution with 60% marks (55% in case of SC/ST). 80% seats are reserved for candidates who have qualified GPAT and passed B. Pharmacy examination of Guru Nanak Dev University. However, if eligible candidate(s) are not available under above category, the vacant seats shall be open to the candidates who have qualified GPAT and B.Pharm. examination from other universities. Mode of Admission The admission will be made, in the order of preference for specialization, on the basis of score in the GPAT and in case of non-availability of GPAT qualified candidates the admission will be based on merit in the Entrance Test to be conducted by the Department. GPAT qualified candidates must indicate their GPAT score in admission form under the column "Any other Qualification". Syllabus for test Important Note: The Entrance Test will be based on multiple choice questions and carry 100 marks and no negative marking. Natural Products: Pharmacognosy & Phytochemistry – Chemistry, tests, isolation, characterization and estimation of phytopharmaceuticals belonging to the group of Alkaloids, Glycosides, Terpenoids, Steroids, Bioflavanoids, Purines, Guggul lipids. Pharmacognosy of crude drugs that contain the above constituents. Standardization of raw materials and herbal products. WHO guidelines. Quantitative microscopy including modern techniques used for evaluation. Biotechnological principles and techniques for plant development, Tissue culture. Pharmacology: General pharmacological principles including Toxicology. Drug interactions. Pharmacology of drugs acting on Central nervous system, Cardiovascular system, Autonomic nervous system, Gastro intestinal system and Respiratory system. Pharmacology of Autocoids, Hormones, Hormone antagonists, chemotherapeutic agents including anticancer drugs. Bioassays, Immuno Pharmacology. Drugs acting on the blood & blood forming organs. Drugs acting on the renal system. Medicinal Chemistry: Structure, nomenclature, classification, synthesis, SAR and metabolism of the following category of drugs, which are official in Indian Pharmacopoeia and British Pharmacopoeia. Introduction to drug design. Stereochemistry of drug molecules. Hypnotics and Sedatives, Analgesics, NSAIDS, Neuroleptics, Antidepressants, Anxiolytics, Anticonvulsants, Antihistaminics, Local Anaesthetics, Cardio Vascular drugs – Antianginal agents Vasodilators, Adrenergic & Cholinergic drugs, Cardiotonic agents, Diuretics, Antijypertensive drugs, Hypoglycemic agents, Antilipedmic agents, Coagulants, Anticoagulants, Antiplatelet agents. Chemotherapeutic agents – Antibiotics, Antibacterials, Sulphadrugs. Antiproliozoal drugs, Antiviral, Antitubercular, Antimalarial, Anticancer, Antiamoebic drugs. Diagnostic agents. Preparation and storage and uses of official Radiopharmaceuticals, Vitamins and Hormones. Eicosonoids and their application. Pharmaceutics : Development, manufacturing standards Q.C. limits, labeling, as per the pharmacopoeal requirements. Storage of different dosage forms. New drug delivery systems. Biopharmaceutics and Pharmacokinetics and their importance in formulation. Formulation and preparation of cosmetics .Pharmaceutical calculations. Pharmaceutical Jurisprudence: Drugs and cosmetics Act and rules with respect to manufacture, sales and storage. Pharmacy Act. Pharmaceutical ethics. Pharmaceutical Analysis: Principles, instrumentation and applications of the following: Absorption spectroscopy (UV, visible & IR). Fluorimetry, Flame photometry, Potentiometry. Conductometry and Plarography. Pharmacopoeial assays. Principles of NMR, ESR, Mass spectroscopy. X-ray diffraction analysis and different chromatographic methods. Biochemistry. Biochemical role of hormones, Vitamins, Enzymes, Nucleic acids, Bioenergetics. General principles of immunology. Metabolism of carbohydrate, lipids, proteins. Methods to determine, kidney & liver function and lipid profiles. Microbiology : Principles and methods of microbiological assays mentioned in the Pharmacopoeia. Methods of preparation of official sera and vaccines. Serological and diagnostics tests. Applications of microorganisms in Bio Conversions and in the Pharmaceutical industry. Clinical Pharmacy : Therapeutic Drug Monitoring, dosage regimen in pregnancy and lactation, pediatrics and geriatrics, renal and hepatic impairment. Drug – Drug interactions and drug – food interactions, adverse Drug reactions. teratogenicity, prescription writing, clinical trails(Overview), patient counseling. Dates a) Submission of Application : 07.06.2011 to 30.06.2011 b) Entrance Test : 06.07.2011 (2.00 - 4.00 p.m.) c) Admission/Counselling : 14.07.2011 Venue: Department of Pharmaceutical Science, GNDU, Amritsar. Contact No. Coordinator/Head: 0183-2258802-09, 2450601-14 Ext. 3459 Fee (Approximate) Rs. 88,040/-(1st.Sem.) Rs.70,800/-(2nd Sem.)

Thursday, May 19, 2011

A section of medical doctors launches campaign against starting Pharm D course in India

 The validity, necessity and promotion of the pharmacy course, Pharm D is being questioned by a section of the Kerala branch of QPMPA, the national  level organisation of private medical practitioners. 

The association plans to set out a national level agitation against the promotion of the course by arguing that the advancement of the course will reduce the medical importance of the doctors. 

The move against the promotion of Pharm D was already kick-started in Kerala by one Dr Sushama Anil, doctor –cum-owner of a Kozhikode based hospital. The doctor is now engaged in the task of mobilizing doctors from other states to escalate the agitation into the level of a national struggle against Pharmacy Council of India.

Dr Sushama Anil, a member of QPMPA has written an article in the monthly journal of the association in which she says that if the Pharm D is recognized and established by the government, and appointed those graduates in the hospitals as intermediaries between doctors and patients, the doctors community will lose the entire control of the medicines. Making a remark on the Pharm D graduates as ‘pharma doctors’, she says the total control of the drugs will be vested up on these ‘compounders’. According to her, the pharmacists, whether B Pharm, M Pharm or Pharm D, are mere compounders.

The article says that with the introduction of Pharm D, the Pharmacy Council of India is trying to bring back the extinct ‘medical practice compounders into force.' This move of the PCI will pave the way for a tussle between doctors and ‘pharma doctors’ (pharmacists) for power, position and importance in the health sector, the doctor maintains through the article. Her argument is that the doctors should be the backbone of the healthcare system, nobody should be allowed to try to be at par with the doctors.

According to her, the pharmacists (‘pharma doctors’) are vested with the roles of conducting patient’s medication history review, medication order review, patient counselling, adverse drug reaction monitoring, therapeutic drug monitoring, ward rounds and providing drug information to the drug information centre, these are nothing to do with the pharmacists, but are the duties of the doctors.  In such a situation, no medical representatives will approach the doctors and their knowledge about the new drugs cannot be updated. This will adversely affect in such a way that the doctors need only to diagnose or carry out the clinical procedures. “MBBS should be renamed as DBBS—Bachelor of Diagnosis and Bachelor of Surgery,” the doctor said.

Since there is the term ‘Doctor’ in the expansion of Pharm D, the person having the Pharm D qualification can use ‘Dr’ as prefix to his name. This is against the dignity of the doctors and the medical profession. Pharm D course is like the ‘old wine in new bottle’ as in olden days for want of doctors in rural areas, the compounders used to treat the patients, Dr Sushama wrote in the article.

While speaking to Pharmabiz at the QPMPA national seminar in Thiruvananthapuram, Dr Sushma Anil said a pharmacist or a compounder cannot become a doctor, then why should he put the term ‘Doctor’ as prefix to his name. The doctor prefers to call the Pharm D graduates as ‘compounders’ rather than calling them as pharmacists. To support her argument, she asks whether a conductor can do the job of a driver. She is of opinion that even the doctors are old in age, they update their knowledge, but the compounders are not. Further she said the doctors are service oriented, but the pharmacists are business oriented. 

While arguing for the dignity of the doctors community, she said the Pharmacy Council of India has started the course on ego basis. “They (pharmacists) want to become above the doctors.”

Another allegation levelled against PCI, according to the article, is that the PCI’s intention is to phase out gradually the three year B Pharm course by giving opportunity for the ongoing Pharmacy graduates to attain Pharm D.

The article also exhorts the doctors’ community to organize and fight together against the launching of the 3.5 year Rural Medical Services (BRMS).

Source: Pharmabiz

Eight candidate drugs under advanced stages of development in CDRI

 As many as eight candidate drugs including those for diabetes and malaria are under advanced stages of development in the Central Drugs Research Institute (CDRI), Lucknow. The premier institute also could identify eight potential leads through researches during the last financial year.

According to the summary of work done during the last financial year, a candidate drug (CDR 134D123) against diabetes has gone through the phase-I single and multiple dose studies. Report has been submitted to AYUSH department and has been referred to Extra Ayurvedic Pharmacopoeia Committee for inclusion. It has been licensed to Mumbai-based TVC Sky Shop for commercialisation.

The phase-III clinical trials have been completed at CSSMU, Lucknow and Seth GS Medical College and KEM Hospital, Mumbai for the candidate drug Picroliv against liver disorder. It has been transferred to DIL, Mumbai, the report said.

The permission for extended clinical trials is being awaited from the DCGI for the candidate drug called 80-574+Atorvastatin, licensed to Cadila Pharmaceuticals, for treating dyslipidemia. Two candidate drugs against malaria are also at advanced stages of development. The drug '97-98', licensed to IPCA Labs of Mumbai has already gone through phase-I single dose clinical study. DCGI has approved for single dose pharmacokinetic study in healthy volunteers as per revised protocol. Pre-clinical data under compilation for IND submission for another anti-malarial drug '99-411' also transferred to IPCA, according to the report.

Modified dossier has been submitted to DCGI with regard to a candidate drug 'CDR 134F194', licensed to TVC Sky Shot Ltd, aimed at treating diabetes and dyslipidemia. The CDRI is also preparing IND application for a herbal candidate drug against stroke. This has been already transferred to Themis Medicare Ltd, Mumbai for commercialisation, the report said.

The CDRI also has identified leads towards developing drugs to treat osteoporosis, bone fracture, diabetes, thrombosis, cancer and tuberculosis. Single dose toxicity study in rat and mice by oral route was completed in the case of `S-007-1500’ to treat osteoporosis and collaboration with industry partner was under negotiation. Likewise, '914-K058' in the same therapeutic category was also in a similar stage of development. Six other leads identified by the institute are open for licensing still, the report said.

Source: Pharmabiz

Cleveland BioLabs to receive US patent for CBLB502 and CBLB612

 Cleveland BioLabs, Inc. announced that it has received a Notice of Allowance from the US Patent and Trademark Office for its Protectan CBLB502 US Patent Application Number 11/722,682, titled “Flagellin Related Polypeptides and Uses Thereof.” Allowed claims cover composition of matter and use of CBLB502 for protecting a mammal from radiation. 

The US Patent and Trademark Office also issued a Notice of Allowance for the company’s Protectan CBLB612 patent application number 11/917,494, titled “Methods of Protecting against Apoptosis using Lipopeptides.” Allowed claims cover the various properties of Protectan CBLB612 and related compounds, including composition of matter and methods of use for protecting against apoptosis.

Yakov Kogan, PhD, MBA, chief operating officer of Cleveland BioLabs, stated, “We are pleased to see the patent portfolio protecting our compounds and technology continue to expand in the US and around the world. These patents validate our unique approach to protection of healthy tissues from the impact of radiation and other acute stresses.”

The company also announced receipt of a Notice of Allowance from the New Zealand patent authority for a patent covering the various properties of Protectan CBLB612 and related compounds, including composition of matter and methods of use for protecting against apoptosis, as well as issuance of a patent for Protectan CBLB612 from the patent authority of South Africa, titled “Method for Increasing and Mobilizing Stem Cells.”

CBLB502 is a rationally–designed, bio-engineered derivative of a microbial protein that potentially reduces injury from acute stresses, such as radiation and chemotherapy, by mobilizing several natural cell protective mechanisms, including inhibition of programmed cell death (apoptosis), reduction of oxidative damage and induction of regeneration-promoting cytokines.

CBLB502 is being developed by Cleveland BioLabs under the FDA’s Animal Efficacy Rule to reduce the risk of or prevent death following total body irradiation during or after radiation disaster. This approval pathway requires demonstration of efficacy in representative animal models and safety, pharmacokinetic, pharmacodynamic and biomarker testing in healthy human subjects.

Evidence of CBLB502's mechanism of action and activity in animal models was published in Science Magazine in April 2008 (Science, 2008, vol. 320, pp. 226-230). Data from 150 healthy human subjects in two phase I safety and tolerability studies indicated that administration of CBLB502 resulted in a rapid and potent cytokine and hepatic immunologic response, similar to that seen in previously conducted non-human primate studies. The most frequent adverse event associated with CBLB502 administration was a transient flu-like syndrome, which generally resolved within 24 hours.

CBLB502 was granted Fast Track and Orphan Drug designations from the FDA for reducing the risk of or preventing death following total body irradiation during or after radiation disaster. The FDA Fast Track programme is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Such programmes include expanded communications (both verbal and written), rolling BLA submission and reviews, priority review (6 month action date instead of 10 month action date) and accelerated drug approval (approval on the basis of a surrogate endpoint). The FDA orphan drug programme provides incentives for sponsors to develop products for rare diseases. Such incentives include extended marketing exclusivity, waiver of BLA filing user fees, grant funding to defray the cost of clinical testing, tax credits for the costs of clinical research and assistance in clinical research study designs.

CBLB612 is a proprietary synthetic agent which has demonstrated the ability to stimulate hematopoietic stem cells and mobilize them into peripheral blood in mouse and primate studies in amounts exceeding documented results of currently marketed drugs. Potential applications for Protectan CBLB612 include accelerated hematopoietic recovery during chemotherapy, as well as during donor preparation for bone marrow transplantation.

Cleveland BioLabs, Inc. is a drug discovery and development company leveraging its proprietary discoveries around programmed cell death to develop treatments for cancer and protection of normal tissues from exposure to radiation and other stresses.

Source: Pharmabiz

Lincoln Pharma launches anti malarial drug ‘ARH 1’

 Lincoln Pharmaceuticals (LPL), Ahmedabad based pharma company, has launched  anti malarial drug ‘ARH 1’, developed using innovative technology known as Dose Optimization Technology under the Novel Drug Delivery System (NDDS). While mainstay treatment for malaria is complex and difficult to administer, ARH 1 is simpler and much more yielding making it easier for malarial patients to tolerate and recuperate from this disease.  ARH 1 will be particularly helpful for the treatment of severe malaria, Falciparum. The drug is more effective with less volume, less pain and low viscosity providing better compliance to malarial patients. The company has applied for a patent of ‘ARH 1’ in India as well as internationally.

Every year, millions in India alone fall victim to malaria, out of which 50 per cent of the cases are Falciparum Malaria; the most dangerous and life threatening form of malaria. ARH 1 will be available in injection form making it the Drug of Choice for the treatment of Malaria. ARH 1 contains Arteether 150mg/ml (Arteether is a fast acting blood schizonticidal agent that kills malarial parasite) and is manufactured using an innovative solubility technique which gives patients suffering from malaria the desired results. The launch of the ARH 1 injection will provide better treatment to millions of Indian’s suffering from the disease.

LPL conducted multi-centric trials on the efficacy and safety of the new and innovative ARH 1 injection at leading hospitals across the country. Clinical trials on more than 280 patients have proven the efficacy of this product in comparison to leading brands available in the market.

Speaking on the occasion Mahendra G Patel, MD, said, “Lincoln Pharma is about providing healthcare for all, the launch of ARH 1is yet another innovative drug that has been created in line with our mantra and we are very excited about its introduction. With ARH 1 we are now the first company in India to provide an enhanced treatment for severe malaria. We at Lincoln Pharma are very happy to be a part of making lives of malarial patients easier with better healthcare products. ARH 1 will further strengthen our position in the Indian pharmaceutical industry and will go a long way in establishing Lincoln Pharma as one of the leading players in the industry”.

Source: Pharmabiz

Foundation Medicine enters clinical cancer genomics collaboration with Celgene

 Foundation Medicine, Inc., a personalized cancer diagnostics company that aims to bring comprehensive cancer genome analysis to routine clinical care, announced a strategic collaboration with Celgene Corporation. The collaboration – Foundation Medicine’s second major pharmaceutical company alliance in 2011 – is focused on using Foundation Medicine’s comprehensive clinical cancer genomics test in ongoing trials of Celgene drug candidates.

The test in development will be used to facilitate faster recruitment of target patient populations and for broad genetic characterization of all trial enrollees which may help to identify those patients most likely to respond to Celgene drug candidates. Financial details of the agreement were not disclosed. 

“We look forward to working with Foundation Medicine and believe their cancer genome analysis platform has the potential to enhance the delivery of personalized care for cancer patients,” said Raj Chopra, MD, PhD, head of translational medicine, Celgene. “The information that Foundation Medicine will provide has the potential to make the drug development process faster and more efficient, enabling us to identify sub-groups of patients in clinical trials who may benefit from our therapies and improve overall outcomes.”

Foundation Medicine’s comprehensive genomic test will use Next-Generation Sequencing (NGS) to analyse routine clinical specimens (i.e., small amounts of paraffin-embedded tumour) for molecular alterations in more than 200 cancer-related genes. The test will be optimized for clinical-grade analysis of tumour tissues, overcoming multiple complexities (such as purity, ploidy and clonality) inherent to tumour genomes. 

The company is working to translate this capability into clinically relevant tests for pathologists and oncologists and expects to obtain CLIA certification as it works to build its cancer diagnostic testing platforms. Test results will be reported through a secure, interactive website linking genomic data to a structured knowledge-base of relevant, publicly available scientific and medical information. Patients whose cancers have specific genetic alterations are often very difficult to recruit for clinical trials, so the company also aims to provide information on relevant clinical trials through its website. By combining genomic data and scientific and medical information in an easy-to-use format, Foundation Medicine seeks to help physicians make the best possible treatment recommendations for each patient.

This announcement follows the recent appointment of Michael J Pellini, MD, to the position of president and chief executive officer at Foundation Medicine. Dr Pellini joined the company from Clarient, a GE Healthcare Company, where he was president and chief operating officer. 

“We are very excited to announce this collaboration with Celgene, which marks Foundation Medicine’s second pharmaceutical industry alliance this year,” said Dr Pellini. “In addition to our collaborations with Celgene and Novartis, Foundation Medicine plans to leverage the breadth and quality of our cancer genome analysis platform to provide a high-quality test for clinical use. We are building significant momentum toward our goal of making personalized cancer treatment a reality for physicians and their patients through the continued strengthening of our senior management team and through collaborations with pharmaceutical companies and academia.” 

Foundation Medicine is dedicated to the development of a comprehensive diagnostic test that improves cancer care by helping physicians personalize treatment for their patients.

Source: Pharmabiz

Tuesday, May 17, 2011

Coffee drinking can reduce the risk of breast cancer

 Researchers found that heavy consumption of coffee reduced the incidence of malignant tumours in breasts by 20 per cent.

In the less common type of the disease – known as ER negative – the effect was even greater with incident rates reduced by half for coffee drinkers compared with non-coffee drinkers.

The researchers said they were unsure as the reasons why it had such an effect although earlier studies have suggested that it could be because it is rich in antioxidants.

For the research, the team from the Karolinska Institutet, in Sweden, looked at the records of nearly 5,000 women over the age of 50, roughly half of which had breast cancer.

They looked at their coffee consumption and found that those who drank more than five cups a day had a reduction of 20 per cent overall in the risk of getting breast cancer.

When they were screened for different types of cancer they found that it had the biggest reduction in ER-negative of 57 per cent.

ER-negative cancer is rare but it is also very hard to treat.

Each year 45,000 women are diagnosed with breast cancer, a third of whom will go on to die from the disease.

The results were published in the journal Breast Cancer Research.

Source: The Telegraph

Sugar makes the medicine work better

 Researchers found that taking antibiotics with sugar could dramatically improve their effectiveness against stubborn infections such as tuberculosis.

Laboratory tests showed that glucose and fructose - a type of sugar found in plants - stimulated bugs and made them more vulnerable to drug treatments.

Professor James Collins, from Boston University, said: "You know the old saying: 'a spoonful of sugar makes the medicine go down? This is more like 'a spoonful of sugar makes the medicine work'."

Chronic and recurrent infections often occur when bacteria shut down and become metabolically dormant.

This allows the bugs, known as "persisters", to dodge the effects of antibiotics.

Over the course of weeks or months, the bacteria return to life, often stronger and more aggressive than they were before, and the patient relapses.

Persistent bugs are different from those that develop antibiotic resistance through genetic mutations, but may be just as much of a problem.

Bacterial resistance can stretch illnesses out over months and cause infections to spread to kidneys and other organs.

The scientists looked at a new way of tackling persistent bacteria by rousing them from hibernation using a simple weapon, sugar.

They found that sugar acts as a stimulant that switches on normal bacterial responses, rendering the bugs vulnerable to antibiotic attack.

Testing the strategy on Eschericia coli (E. coli) bacteria, a common cause of urinary infections, the researchers were able to eliminate 99.9 per cent of persisters within just two hours.

Without sugar, the drugs they used had no effect.

The approach, reported in the journal Nature, was similarly effective against persistent Staphylococcus aureus bacteria, which can produce serious infections.

Prof Collins now plans to investigate whether sugar additives can improve the effectiveness of drugs against tuberculosis (TB).

TB is a chronic lung infection responsible for more deaths worldwide than any other infectious disease.

Each day around 4,700 people die from the effects of TB, according to the World Health Organisation.

"Our goal was to improve the effectiveness of existing antibiotics, rather than invent new ones, which can be a long and costly process," said Prof Collins' Boston University colleague, Kyle Allison, who was the first author on the study.

The findings have the potential to improve the lives of untold numbers of people who struggle with nagging infections, while also reducing healthcare costs substantially, he added.

Source: The Telegraph

Musical training boosts memory and hearing

 Researchers found that musicians are more likely to keep their memories active and also their hearing in tact.

They believe that the training helps your brain be more adaptable to ageing and make adjustments for any decline in the ability to remember or ability to separate speech from background noise.

The findings add further weight to the benefits of musical training which is also associated with greater learning ability in the classroom,

The study co-author Dr Nina Kraus, at Northwestern University, in Chicago, said: "Lifelong musical training appears to confer advantages in at least two important functions known to decline with age – memory and the ability to hear speech in noise.

"Difficulty hearing speech in noise is among the most common complaints of older adults, but age-related hearing loss only partially accounts for this impediment that can lead to social isolation and depression.

"It's well known that adults with virtually the same hearing profile can differ dramatically in their ability to hear speech in noise."

To find out why, researchers at the Auditory Neuroscience Laboratory, made 18 musicians and 19 non-musicians, aged 45 to 65, carry out a number of tests for speech in noise, memory and processing ability.

The musicians – who began playing an instrument at age nine or earlier and consistently played an instrument throughout their lives – beat the non-musician group in all tests except one where they showed nearly identical ability.

Doctor Kraus said the experience of extracting meaningful sounds from a complex soundscape – and of remembering sound sequences – enhances the development of auditory skills.

She said: "The neural enhancements we see in musically-trained individuals are not just an amplifying or "volume knob" effect.

"Playing music engages their ability to extract relevant patterns, including the sound of their own instrument, harmonies and rhythms."

Dr Kraus said music training "fine-tunes" the nervous system.

She said: "Sound is the stock in trade of the musician in much the same way that a painter of portraits is keenly attuned to the visual attributes of the paint that will convey his or her subject.

"If the materials that you work with are sound, then it is reasonable to suppose that all of your faculties involved with taking it in, holding it in memory and relating physically to it should be sharpened.

"Music experience bolsters the elements that combat age-related communication problems."

The study was published in the journal PLoS One.

Source: The Telegraph

Binge drinking damages the memory of people as young as 18

 Researchers have found that a big night out destroys long term memory even in young adults.

They believe that heavy alcohol consumption makes it more difficult to build new memories because the hippocampus, an area at the centre of the brain, which plays a key role in learning and memory, is very susceptible to its poisonous effects.

It is a particularly worrying finding as binge drinking is a growing problem in Britain and other European countries – particularly in the young and those at university.

The Spanish study of university students found binge drinking affects declarative memory – a form of long-term memory – with the undergraduates showing a reduction in ability to learn new information given to them verbally.

On a sliding scale they scored lower in two tests designed to see how much knowledge they retained and recalled.

Researcher Dr Maria Parada at the Universidade de Santiago de Compostela said: "In northern European countries, there is a strong tradition of a sporadic, drunkenness-orientated, drinking style.

"In contrast, countries on the Mediterranean coast, such as Spain, have traditionally been characterised by a more regular consumption of low doses of alcohol.

"In recent years, the pattern of binge drinking among young people has become more widespread throughout Europe, hence the growing concern about this issue.

"I think it´s important to examine alcohol´s effects on the hippocampus because in animal studies, particularly in rats and monkeys, this region appears sensitive to the neurotoxic effects of alcohol, and this structure plays a main role in memory and learning

"In other words, binge drinking could affect memory of young adults, which might affect their day-to day lives.

The study examined 122 Spanish university students aged 18 to 20 years of age divided into two groups – those who engaged in binge drinking and those that abstained.

They were then subjected to a neuropsychological assessment which included recalling visual and verbal experiences.

Dr Parada said: "Our main finding was a clear association between binge drinking and a lower ability to learn new verbal information in healthy college students, even after controlling for other possible confounding variables such as intellectual levels, history of neurological or psychopathological disorders, other drug use, or family history of alcoholism.

"Whereas most attention has focused on negative consequences such as traffic accidents, violence or public disorder, society and students themselves are unaware of the damaging effects binge drinking may have on the brain.

The findings are published in Alcoholism: Clinical & Experimental Research.

Source: The Telegraph

DNA decoded: Depression is hereditary

 LONDON: Scientists say they have discovered the first solid evidence that variations in some peoples' genes may cause depression - one of the world's most common and costly mental illnesses. 

In a rare occurrence in genetic research, a Britishled international team's finding of a DNA region linked to depression has been replicated by another team from the US who were studying a separate group of people. 

The researchers said they hoped the findings would bring scientists closer to developing more effective treatments for depression . "These findings will help us track down specific genes that are altered in people with this disease," said Gerome Breen of King's College London's Institute of Psychiatry , who led one of the studies.

 

Source: Times of India

A simple blood test to tell how long you will live

 A blood test that can show how fast someone is aging - and offers the tantalising possibility of estimating how long they have left to live - is to go on sale to the general public in UK later this year. 

The controversial test measures vital structures on the tips of a person's chromosomes, called telomeres, which scientists believe are one of the most important and accurate indicators of the speed at which a person is aging. 

Scientists behind the £435 test said it will tell whether a person is biologically aging, as measured by the length of their telomeres, and is older or younger than their actual chronological age, as measured by years since birth. 

The scientists, however, do not yet believe they can narrow down the prediction to calculate the exact number of months and years a person has yet to live. They do not yet believe the information could be used to calculate the exact number of years a person has left to live, but several studies have indicated that individuals with shorter-thannormal telomeres are likely to die younger than those with longer telomeres. 

Medical researchers believe that telomere testing will become widespread within the next five or 10 years, but there are already some scientists who question its value and whether there should be stronger ethical controls over its wider use. 

In addition to concerns about how people will react to a test for how old they really are, some scientists are worried that telomere testing may be hijacked by unscrupulous organisations trying to peddle unproven anti-aging remedies and other fake elixirs of life. 

The results of the tests might also be of interest to companies offering life-insurance policies or medical cover that depend on a person's lifetime risk of falling ill or dying prematurely. 

However, there is a growing body of respectable scientific opinion that says testing the length of a person's telomeres could provide vital insights into the risk of dying prematurely from a range of age-related disorders , from cardiovascular disease to Alzheimer's and cancer. 

"We know that people who are born with shorter telomeres than normal also have a shorter lifespan," said Maria Blasco of the Spanish National Cancer Research Centre in Madrid, who is the inventor of the new commercial telomere test. "But we don't know whether longer telomeres are going to give you a longer lifespan. That's not really known in humans." 

"What is new about this test is that it is very precise. We can detect very small differences in telomere length and it is a very simple and fast technique where many samples can be analysed at the same time. Most importantly, we are able to determine the presence of dangerous telomeres - those that are very short." 
Blasco's company, Life Length, is in talks with companies across Europe to market the test and collect blood samples for analysis. 

Source: Times of India

Surgical Procedure Appears to Enhance Smiles in Children With Facial Paralysis

 Transferring a segment of muscle from the thigh appears to help restore the ability to smile in children with facial paralysis just as it does in adults, according to a report in the May issue of Archives of Facial Plastic Surgery, one of the JAMA/Archives journals. The article is part of a theme issue focusing on facial plastic surgery in the pediatric population.

Facial paralysis often disrupts the ability to smile. In pediatric patients, this can be especially problematic, according to background information in the article. Surgery to repair the affected area may generate failure rates as high as 30 percent. But not acting can also harm children, the authors write: "The inability to express oneself via facial movement can have serious social consequences because it is the dominant nonverbal expression of happiness and contentment. The additional functional and esthetic issues associated with facial paralysis can be devastating to a child's development, or to their recovery following treatment for a central nervous system (CNS) tumor resulting in facial paralysis."

Tessa A. Hadlock, M.D., and colleagues from the Massachusetts Eye and Ear Infirmary, Boston , evaluated pediatric patients undergoing free gracilis transfer (an operation in which part of the gracilis muscle in the thigh is transplanted into facial muscles). They compared 17 children with facial paralysis who had a total of 19 surgeries to 17 adults who also had 19 of the same surgeries. The authors explain that they wanted to determine failure rates in children, discover how much smiles and quality of life (QOL) improved after the operation, and examine whether these patients' experiences differed from those of adults. "These data were sought under the hypothesis that establishing a QOL benefit would help clinicians and families make more insightful decisions regarding surgery."

The main measure of smile improvement was the extent of commissure excursion (movement of the corners of the mouth). The average change in pediatric patients was 8.8 mm, which is similar to the change that adults experienced. The researchers determined that the surgery failed in two of the pediatric patients (11%) versus in four of the adults (21 percent). Thirteen children completed both a pre-operative and a post-operative QOL measure, the Facial Clinimetric Evaluation (FaCE); the results show a statistically significant QOL improvement after the free gracilis transfer.

"In conclusion," the authors write, "free gracilis for smile reanimation in children carries an acceptable failure rate, significantly improves smiling, and seems to improve QOL with respect to facial function." They add, "Early facial reanimation provides the advantage of permitting children to express themselves nonverbally through smiling and may in fact lead to fewer negative social consequences as they interact with peers.

Source: ScienceDaily

Genomic Archeology Reveals Early Evolution of Sex Chromosomes

 A team from Uppsala University, Uppsala, Sweden, is using genomics to shed light on the early evolutionary history of sex chromosomes. The research is published in the April 2011 Eukaryotic Cell.

Among other things, the genome is a place where the distant past can be investigated. Researchers have used it most notably to trace the relationships among species far more accurately than can be done with conventional methods.

Sex chromosomes in animals are so ancient -- in the hundreds of millions of years old--that they retain few traces of the historical events that drove their evolution. But the researchers had found in earlier studies that the mating type chromosomes in the self-fertilizing fungus, Neurospora tetrasperma, which are analogous to X and Y in sexually reproducing organisms, have a region of suppressed recombination that is roughly as recent as the split between chimpanzees and hominins -- less than six million years old.

Suppressed recombination preserves the genomic landscape, because normally, chromosomes recombine during mating, which shuffles the genes like a deck of cards. But suppressed recombination also interferes with natural selection, by forcing genes to be selected or deselected in packages, like the packages of options on new cars that force you to buy the navigation system, the satellite radio, and the MP3 system if you want the side curtain airbags.

The Uppsala researchers' major discovery is that many preferred codons disappeared from regions of the mating type chromosomes where recombination was suppressed. Codons are the "words" of the genetic code. Different codons code for each of the 20 amino acids used in living systems. They code for amino acids, which are the building blocks of proteins, the molecules that form both most of the structure, and most of the machinery cells. Like words in human language, codons often have synonyms. But "Many organisms studied to date preferentially use a specific set of preferred codons which are believed to promote efficient and accurate protein synthesis," says corresponding author Hanna Johannesson. Thus, they are known as "preferred codons."

The suppressed recombination the researchers had found earlier in N. tetrasperma is accompanied by the loss of these preferred codons.

Beyond this, "Our study furthers the understanding of factors driving mutational changes in genomes, which is a key issue in medical and natural science," says Johannesson. "For example, the onset of mutations, and the ability, or inability of organisms to eliminate them from their genome underlie key processes such as the onset of diseases in animals, and the rate of species extinctions. Our study advances the understanding of when and how young regions of suppressed recombination in sex regulating chromosomes accumulate mutations, and why evolution may fail to remove these harmful changes in an efficient manner."

Source: ScienceDaily

New Prostate Cancer Test More Specific, Sensitive Than PSA Test

 A new test for prostate cancer that measures levels of prostate specific antigen (PSA) as well as six specific antibodies found in the blood of men with the disease was more sensitive and more specific than the conventional PSA test used today, according to a study by researchers at UCLA's Jonsson Comprehensive Cancer Center.

The test, called the A+PSA assay, also reduced the rate of false-positives, tests that indicate the presence of cancer when no disease is actually present, said Gang Zeng, an associate professor of urology, a Jonsson Cancer Center researcher and senior author of the study.

"This is a very promising new approach," Zeng said. "Instead of using just one parameter, PSA, to test for prostate cancer, we use multiple parameters that can be measured in a single reaction."

The study appears in the May issue of the peer-reviewed Journal of Translational Medicine.

The conventional PSA test for prostate cancer has been used for nearly 30 years and is not specific enough in delineating between malignancies and non-malignant diseases of the prostate, such as benign prostatic hyperplasia (BPH), an enlarging of the prostate common in aging men that increases PSA levels, Zeng said.

The retrospective study used blood taken before surgery from 131 patients from UCLA, Japan and France with biopsy-confirmed prostate cancers and compared results to blood taken from 121 men with either BPH or prostatitis, an infection or inflammation of the prostate that increases PSA levels. The study focused on six specific prostate-cancer associated antigens -- NY-ESO-1, SSX-2,4, XAGE-lb, AMACR, p90 and LEDGF -- which are found predominantly in patients with prostate cancer and not in benign prostate conditions.

The A+PSA assay looked simultaneously for PSA and antibodies to the six prostate-cancer associated antigens in a single reaction test done in a laboratory, much like PSA is measured. The new test takes about two hours, again similar to the PSA test. The test results in an index of numbers used to diagnose cancer, with a score of 0 to 0.5 indicating a benign result and 0.5 to 1 indicating the presence of prostate cancer, Zeng said.

In the new test, sensitivity -- the percentage of men with prostate cancer who were correctly identified as having a malignancy -- was 79 percent compared to the 52 percent found in PSA testing. Specificity -- the percentage of healthy men who were correctly identified as not having prostate cancer -- was 84 percent compared to the 79 percent found when testing for PSA alone.

The rate of false-positives using conventional PSA testing is 21 percent. With the new A+PSA assay, the false-positive rate is 16 percent, Zeng said.

"Science has improved so much since the PSA test was developed and I think it's time for a more specific and sensitive test to be developed," Zeng said. "I think we have a test that has great potential to improve the diagnosis of prostate cancer. I knew it would be better than the classic PSA test, but I was amazed at how much better it really was in this study."

Dr. Allan Pantuck, an associate professor of urology, Jonsson Cancer Center researcher and a study author, said a more specific and sensitive test for prostate cancer would be a welcome addition to the diagnostic tool box.

"While measuring PSA is useful in identifying men with prostate cancer, some men with prostate cancer have a normal PSA level and small elevations in PSA above normal may be produced both by prostate cancer as well as an enlarged but benign prostate," Pantuck said. "Combining PSA with a panel of tests that measure an individual man's anti-cancer immune response may better identify who has prostate cancer and who can be spared an unnecessary invasive biopsy."

Zeng and his team are working now to adjust and improve the statistical index used in their test to generate the "score." He'd like to do a prospective study that would include the racial, ethnic and age information for each man who provides blood. The test could perhaps be altered for men over a certain age if the antibody levels found in their blood vary. African-American men may also have varying levels of the six antibodies. There also are additional antibodies that could be added to the assay that may improve both the sensitivity and specificity of the test, Zeng said.

"Different men may have different levels of the six antibodies or different antibodies all together based on their race, age and ethnicity," Zeng said. "We want as accurate an assay as we can possibly develop."

Any new prostate cancer test would have to be approved by the U.S. Food & Drug Administration.

The study was funded in part by the Prevent Cancer Foundation, the National Institutes of Health and the National Cancer Institute Early Detection Research Network

Source: ScienceDaily

MSN plans to launch four drugs in current financial year in domestic market

 The Hyderabad-based MSN Laboratories, a manufacturer of both formulations and Active Pharmaceutical Ingredients (APIs), is planning to launch four drugs during the current financial year in the domestic market.

According to the company, the products will be in the therapeutic areas such as neurology, cardiology and Central Nervous System (CNS). The company is waiting for the approval from the Drugs Controller General of India (DCGI) to launch the products in the Indian market. It said that all the four drugs would be marketed for the first time in India.

Speaking to the reporters after the launch of Tapal, a novel, centrally acting analgesic for the management of moderate to severe acute pain, Dr M S N Reddy, chairman and managing director, MSN Laboratories, said, “We are looking forward to launch 10 to 12 molecules every year and will cover therapeutic areas such as diabetic, pain management, etc. By launching Tapal, we aim to provide quality product at affordable price to the people.” He added that the cost of the product is one-fifth of its branded version.

The company said that it’s an in-house developed product and is launching for the first time in India. It marked MSN Laboratories’ foray into approximately Rs.3500 crore pain management market. The company, which is marketing the product, may also give it to a few companies for co-marketing in the future.

The company, with focus on the domestic, Asia-Pacific, Latin America and CIS markets, will offer Custom Research And Manufacturing Services (CRAMS) with the completion of its research and development centre in Hyderabad. It is making an investment of Rs.100 crore in the centre. The company is also considering acquisitions in the future when situation arises.

Source: Pharmabiz

Pacira Pharma to present positive results from its phase III study evaluating Exparel at ASCRS 2011 annual meeting

 Pacira Pharmaceuticals, Inc., an emerging specialty pharmaceutical company, announced that positive results from its phase III study evaluating Exparel in patients following hemorrhoidectomy will be presented at the 2011 American Society of Colon and Rectal Surgeons (ASCRS) Annual Scientific Meeting in Vancouver, British Columbia. Results from this multi-centre, randomized, double-blind, parallel-group, placebo-controlled study demonstrated that patients experienced less pain and a reduction in opioid use for 72 hours following a single injection of Exparel at the end of the surgical procedure. This is the first time this study data has been presented at a major North American medical meeting.

The poster presentation, titled “Extended-Release Multivesicular Liposome Bupivacaine (Exparel) Is Superior to Placebo for Post-Hemorrhoidectomy Pain Reduction,” will be presented by Dr Stephen R Gorfine, clinical professor of surgery in the Division of Colorectal Surgery at The Mount Sinai Medical Centre, on Tuesday, May 17, 2011 at 11:30 a.m. EDT.

“These phase III data demonstrate that the median time to first opioid rescue for patients treated with Exparel following hemorrhoidectomy was significantly longer than those treated with placebo,” said David Stack, president and CEO of Pacira Pharmaceuticals. “Patients in this study underwent excisional hemorrhoidectomy using the Milligan-Morgan technique, a painful soft tissue surgery. We believe that these data coupled with our positive phase III data from our bunionectomy trial will help support the potential utility of Exparel in a clinical setting and build important mindshare among key opinion leaders. This is the first time that these phase III data are being presented at a North American medical meeting and we believe this is another important milestone as we execute on our clinical and pre-commercial strategies.”

Some of the key findings of the study includes: the study met its primary endpoint with a statistically significant reduction in cumulative pain score in patients receiving Exparel compared to placebo (p<0.0001). A total of 189 patients were treated at 12 clinical sites in Europe. The percentage of patients who were entirely opioid free was higher (p<0.0008) with Exparel than with placebo. The median time to first opioid rescue was 14 hours and 20 minutes in the Exparel group, more than 10 times longer than the placebo group (1 hour and 10 minutes) (p<0.0001).

Exparel patients consumed statistically significantly less opioid rescue medication through 72 hours compared to the placebo group (p=0.0006). In addition, the study showed that Exparel was well tolerated, with the incidence of Adverse Events (AEs) similar to placebo. GI side effects, commonly associated with opioid use, were reduced in the Exparel group compared to placebo, and there were no Serious Adverse Events (SAEs) reported in patients receiving Exparel. Overall, 94.7% of patients treated with Exparel were “satisfied” or “extremely satisfied” with their post-surgical analgesia at 72 hours compared with 73.9% in the placebo group (p<0.0007).

There were no deaths or withdrawals due to an AE in the study. There was one SAE (mild thrombophlebitis), which occurred in a patient who had received placebo, and was resolved the next day after treatment. The most common AEs experienced were gastrointestinal in nature, occurring in 8.4% of Exparel patients and 13.8% of placebo patients.

Pacira Pharmaceuticals, Inc. is an emerging specialty pharmaceutical company focused on the development, manufacture and commercialization of novel pharmaceutical products, based on its proprietary DepoFoam drug delivery technology, for use in hospitals and ambulatory surgery centres. 

Exparel is Pacira's proprietary drug candidate consisting of bupivacaine encapsulated in DepoFoam, both of which are currently used separately in FDA-approved products. Bupivacaine is a well-characterized anaesthetic/analgesic that has an established safety profile with more than 20 years of use in the United States. The most common adverse events following Exparel administration were nausea, constipation, and vomiting.

Source: Pharmabiz

Sunday, May 15, 2011

Disruption of Nerve Cell Supply Chain May Contribute to Parkinson's

 New data offer hints to why Parkinson's disease so selectively harms brain cells that produce the chemical dopamine, say researchers at Washington University School of Medicine in St. Louis.

Dopamine is involved in brain cell communications including the signals that control movement. As Parkinson's kills the dopamine-producing cells, patients begin to develop tremors, problems moving and other symptoms.

The new research shows that a drug known to damage dopamine-producing nerve cells and mimic Parkinson's disease does so by rapidly damaging cellular energy generators called mitochondria. This damage impairs the ability of mitochondria to circulate around the cell as they normally would. As a result, axons, the extended arms nerve cells use to send messages, wither; a few days later, the body or main portion of the cell also dies.

"Much of the research into Parkinson's disease treatments is focused on saving the bodies of these cells, but our results suggest that keeping axons healthy also is essential,"says Karen O'Malley, PhD, of Washington University School of Medicine in St. Louis. "When axons die back, dopamine is no longer delivered to the neurons that need it. The cell body also has fewer connections to other cells, and it needs those connections to survive."

The results were published May 11 in The Journal of Neuroscience.

Many processes and facilities for cellular maintenance are in the body of the nerve cell, and their products sometimes have to travel a significant distance to reach the axon's end.

"If you think, for example, about one of your peripheral nerves, the cell body is located in the spinal column, but some of the axons extend as far as your big toe," says O'Malley, professor of neurobiology. "That's like the cell body sits in an office in St. Louis and the end of the axon is in Chicago."

O'Malley compares the axon's system for transporting supplies to a railroad. Mitochondria are part of the railroad's cargo. They supply the energy that allows the axon to do its work.

For the study, O'Malley gave cultured mouse nerve cells a toxin called MPP+ that causes Parkinson's-like symptoms.

"MPP+ is a derivative of a synthetic form of heroin developed in California in the early 1980s," O'Malley says. "It came to scientists' attention when teenage abusers of the drug went to the hospital with Parkinson's disease symptoms."

O'Malley found that the toxin stopped the movement of mitochondria in the axon in 30 minutes. The railroad still functioned, shipping other cargo to the end of the axon. But most mitochondria either stopped moving or were headed for the cell body instead of the axon.

O'Malley suspected that this meant the mitochondria were damaged by the changes caused by the toxin and being shipped back to the cell body for repair. Additional tests supported this theory, showing that the mitochondria had lost their ability to maintain their membrane potential, a measure of mitochondrial fitness.

The specificity of this toxin for dopamine-producing cells is reinforced by the finding that other types of nerve cells did not have problems transporting mitochondria after toxin exposure. In a comparison between different nerve cell types, O'Malley found mitochondria in dopamine-producing nerve cells are smaller in size and travel three times slower. But she can't yet definitively say that these distinctions play a role in the problems caused by the toxin.

Scientists screened several compounds to see if they could block the toxin's effects. Only two antioxidants worked, glutathione and N-acetyl cysteine. The latter compound has already been shown to be effective in animal models of Parkinson's disease and is used as a treatment for other disorders in patients.

O'Malley is currently studying whether two genes linked to Parkinson's disease affect mitochondria damaged by the toxin.

"We're going to continue to look for specific differences in these cells that might help scientists develop better treatments," O'Malley says

Source: ScienceDaily

Protein Responsible for the Detection of Extreme Heat and Pain Discovered

 The protein responsible for the detection of extreme heat and pain resulting from infections has been identified by a team of K.U.Leuven researchers led by Professor Thomas Voets. The protein is a promising target for the development of new analgesic medications.

A rapid pain response to extreme temperatures is of vital importance to prevent being burned by touching a hot object or accidentally swallowing scolding soup, for example. Sensory nerves throughout the body -- including in our skin and mucous membranes -- detect temperature. In people who suffer from certain conditions, such as infections or nerve damage, these nerves become extra sensitive. This sometimes results in oversensitivity to innocuous temperatures and chronic pain.

There are ion channels in the cell wall around these nerves -- microscopic sluices that react to certain stimuli and then send electrical signals to the brain. Approximately ten years ago, American researchers discovered the capsaicin receptor: an ion channel that is responsible for the detection of heat and of "hot" chemical substances. Capsaicin is the substance that gives red peppers their spicy taste. Research demonstrated, however, that the capsaicin receptor is not responsible for all heat detection and that there must be other molecular detectors for extreme heat.

Research conducted by Doctor Joris Vriens, in collaboration with colleagues at the Leuven Laboratory for Ion Channel Research and German researchers, has demonstrated that the ion channel TRPM3 is also a molecular sensor for heat and for the hormone pregnenolone sulfate -- a precursor to the gender hormones oestrogen or testosterone. Mice with a defective TRPM3 gene appear to feel far less pain when exposed to heat or the steroid hormone. Moreover, these mice do not develop oversensitivity to heat when they have infections. These new discoveries make TRPM3 a promising target for the development of new analgesic medications

Source: ScienceDaily

Two Defective Proteins Conspire to Impair Nerve Cell's 'Powerhouse' in Alzheimer's Disease

 Two proteins that are abnormally modified in the brains of patients with Alzheimer disease collude, resulting in ill effects on the crucial energy centers of brain cells, according to new findings published online in Neurobiology of Aging.

The research raises the possibility that pathological forms of two proteins, amyloid beta and tau, which make up the pathological hallmarks of the brains of Alzheimer patients -- plaques and tangles -- may work in tandem to decrease the survival of brain cells.

The findings come as part of a bundle of results from several laboratories that are putting cellular components known as mitochondria under increasing scrutiny in the development of a range of brain conditions, including Alzheimer, Huntington and Parkinson diseases.

Mitochondria are like tiny little energy plants inside neurons and other cells, constantly on the move, churning out the energy that cells need to survive. Mitochondria are also master controllers as they perform additional jobs such as keeping calcium levels normal. A cell with damaged mitochondria is unable to produce sufficient energy to keep the cell going, cannot buffer calcium correctly, and releases oxidative molecules that damage the cell. These types of events may be occurring in the Alzheimer disease brain, resulting in nerve cells that don't function properly.

"The idea that amyloid beta and tau may work together to cause mischief in the brain has been an evolving theme among scientists for a number of years," said Gail Johnson, Ph.D., professor of Anesthesiology and the corresponding author of the paper. "The precise relationship between the two pathologies is unclear, but there may be a synergy between the two when it comes to their effects on mitochondria in Alzheimer disease."

Johnson's group took a particularly close look at a pathological form of the protein known as tau, which helps stabilize a network of highway-like tracks called microtubules in neurons. In recent years scientists like Johnson have been focusing on an abnormally shortened form of the protein, known as truncated tau, as one that likely has a role in Alzheimer disease.

Johnson's team looked at the performance of mitochondria in rat neurons during exposure to amyloid beta, to the regular tau protein, to the truncated version of tau, and to combinations of amyloid beta and the two versions of tau. Among the experiments was one in which scientists tracked the movement of mitochondria, snapping a new image every 10 seconds during a five-minute span to track the movements of the organelles within neurons.

The biggest changes to mitochondria occurred when amyloid beta and truncated tau were present together. Effects included:

  • The ability of mitochondria to maintain their electrical potential, which is needed to produce energy efficiently, was severely impaired. They had only one-third of the electrical potential of mitochondria in control cells.
  • Mitochondria usually are highly mobile and distributed throughout the cell. However, in the presence of truncated tau and amyloid beta, mitochondria clumped together abnormally in some parts of neurons and failed to get to other parts of neurons, such as the synapses, like they normally do. Overall, only about half the mitochondria were mobile compared to their counterparts not exposed to the pathological proteins.
  • Cells that were exposed to both truncated tau and amyloid beta were less able than usual to respond to cellular stress. The number of harmful molecules known as reactive oxygen species or free radicals was boosted 60 percent in these cells.
  • Mitochondria exposed to amyloid beta and truncated tau were fragmented, with the average length just half that of normal mitochondria.

The cellular changes that Johnson is looking at likely occur before a patient begins to experience symptoms like memory loss. Most scientists believe that changes in the brains of Alzheimer patients begin years or even decades before the signs of Alzheimer disease become apparent.

"By the time the cells are dead, it's far too late to do much," said Johnson, who is also a professor in the Department of Pharmacology and Physiology and a scientist in the Center for Neural Development and Disease. "Therefore, in the field of Alzheimer research, investigators are looking for early markers and indicators of disease so that patients could be identified before significant nerve cell death has occurred. In addition, studies in many labs are ongoing to identify treatments that could target these early events.

"Perhaps," Johnson adds, "the new information on mitochondrial dysfunction in Alzheimer disease can be used to fight the disease, as it is likely an important target for therapeutic intervention. Given the fact that Alzheimer disease is a very complex disease, a monotherapeutic approach may not be as effective as a combinatorial treatment strategy, as is the case for treating other diseases including cancer and diabetes. Further studies on why and how mitochondria are compromised in Alzheimer disease as well as other neurodegenerative conditions are needed to develop effective treatments which will increase mitochondrial function and improve the health of the brain cells.

Source: ScienceDaily

BioFocus and Astellas Pharma sign CNS drugs discovery agreement

 

BioFocus has signed a collaboration agreement with Astellas Pharma Inc. focused on discovering novel targets in the field of CNS disorders. Under the agreement, BioFocus will utilize its SilenceSelect target discovery platform to deliver validated targets to enhance the Astellas neurology pipeline and will receive research funding and success payments based on the progress of the collaboration.

“We are delighted to support Astellas Pharma in its research” said Dr Chris Newton, SVP Galapagos Services and managing director BioFocus. “Our target discovery offering allows clients to access a unique platform providing rapid identification of novel targets through a proven technology”.

Astellas Pharma Inc., is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. It is committed to becoming a global category leader in urology, immunology including transplantation and infectious diseases, oncology, neuroscience, DM complications and metabolic diseases.

BioFocus aims to expand its partners’ drug pipelines by accelerating the gene-to-drug candidate discovery process. This is achieved through a comprehensive discovery platform, which includes target discovery in human primary cells, focused as well as diverse compound libraries, in vitro and cell-based screening, structural biology, medicinal chemistry, ADME/PK services, supported by unique chemogenomic and informatics tools, and compound library acquisition, storage and distribution services.

 

Source: Pharmabiz

Rockwell Medical receives US patent for SFP packaging & method of use

 

Rockwell Medical a fully-integrated biopharmaceutical company offering innovative products and services targeting End-Stage Renal Disease (ESRD), Chronic Kidney Disease (CKD), and iron deficiency anaemia, announced that it has received notice from the US Patent and Trademark Office for patent issuance that includes product claims that require ferric pyrophosphate dissolved in a bicarbonate solution held in a polyolefin container, such as an HDPE container; and method claims using the claimed product on its proprietary Soluble Ferric Pyrophosphate (SFP), the company's lead-drug candidate for treating iron deficiency anaemia in ESRD patients.

The patent, “Packaging of Ferric Pyrophosphate for Dialysis,” includes product claims that cover ferric pyrophosphate dissolved in a bicarbonate solution held in a polyolefin container, such as an HDPE container; and method claims using the claimed product. The patent provides protection through 2029. Additionally, the patent may be eligible for an extension under 35 USC 156, which is equal to the period of time from patent issuance to FDA approval. Further patent applications are pending.

Robert L Chioini, chairman, CEO and president of Rockwell Medical, stated, “This is another important patent issuance. It further protects SFP against potential infringement in the marketplace and it enables Rockwell to strengthen its intellectual property portfolio.”

Soluble Ferric Pyrophosphate (SFP) is a novel, investigational, continuous iron therapy in late-stage clinical development, designed to treat iron deficiency anaemia in ESRD patients. In contrast to intravenous (IV) iron delivery, SFP is a proprietary, water-soluble iron that travels to the bloodstream and binds directly to apo-transferrin and then travels to bone marrow to assist in forming a healthy red blood cell, similar to normal physiologic dietary iron intake.

SFP is a continuous iron replacement treatment, delivering small doses of iron during every dialysis session, to replenish the 5-7mg of iron lost during the dialysis procedure, thereby maintaining haemoglobin in the target range as per Kidney Disease Quality Outcomes Initiative (KDQOI) recommendations. Clinical trial data to date suggests that SFP, delivered via dialysate during each dialysis treatment, maintains optimal iron balance and avoids liver toxicity while decreasing associated drug administration costs.

Academic studies have shown that more frequent maintenance doses of iron improve therapeutic response to Erythropoiesis-Stimulating Agents (ESA's), thereby decreasing the ESA doses needed to maintain haemoglobin in the target range. Rockwell has licensed exclusive world-wide rights to manufacture and sell SFP and has obtained patent protection for SFP in multiple countries, including the three largest dialysis markets in the world: the United States, Japan, and the European Union. Based on current market data, the US dialysis market for IV iron is approximately $560 million annually while global market potential is approximately $1 billion.

Rockwell Medical is a fully-integrated biopharmaceutical company offering innovative products and services initially targeting ESRD, CKD, and iron deficiency anaemia. An established manufacturer and leader in delivering high-quality haemodialysis concentrates/dialysates to dialysis providers and distributors in the US and abroad, Rockwell provides products that are used to maintain human life by removing toxins and replacing critical nutrients in the dialysis patient's bloodstream. Dialysis is a process that duplicates kidney function for patients who suffer from ESRD. There are approximately 400,000 ESRD patients in the United States. World-wide there are approximately 2 million ESRD patients, growing at an annual rate of 5-6 percent.

 

Source: Pharmabiz

Santaris advances a second drug from its cardiometabolic programme, SPC4955, into phase I trials to treat high cholesterol

 Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, announced that it has advanced a second drug from its cardiometabolic programme, SPC4955 into phase I clinical trials, for the treatment of high cholesterol. Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug Platform, SPC4955 is a mRNA-targeted drug candidate that inhibits apolipoprotein B (apoB), a major protein component involved in the formation of Low Density Lipoprotein Cholesterol (LDL-C) or “bad” cholesterol.

Cholesterol is an essential component of all cells and several important hormones, but cholesterol levels that are out of balance or too high overall lead to the formation of atherosclerotic plaques that cause cardiovascular diseases such as heart attacks or strokes. According to the World Health Organization, cardiovascular disease is the number one cause of death globally and high cholesterol is estimated to cause 18% of strokes and 56% of heart disease globally.

The randomized, dose-escalation, double-blind, placebo-controlled phase I study will assess safety, tolerability, pharmacokinetics, and pharmacodynamics of SPC4955. The study aims to enroll 30 healthy volunteers who will be randomized to receive either subcutaneous injections of SPC4955 or placebo. In preclinical studies, SPC4955 potently and dose-dependently inhibited the synthesis of apoB resulting in significant and durable reductions in plasma levels of LDL-C and triglycerides. 

Last week, Santaris Pharma A/S announced it had advanced another drug candidate, SPC5001, a mRNA-targeted drug inhibiting the synthesis of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), for the treatment of high cholesterol into phase I clinical trials. PCSK9 is a protein involved in removing Low Density Lipoprotein Cholesterol (LDL-C) or “bad” cholesterol from the bloodstream. 

“Advancing two drug candidates, SPC4955 and SPC5001, in the space of only a week from our cardiometabolic programme into the clinic is a testament to the efficiency of our LNA Drug Platform and Drug Discovery Engine capabilities and represents an important step for patients as multiple approaches are needed to lower high cholesterol levels,” said Arthur A. Levin, PhD, vice president and chief development officer of Santaris Pharma A/S. “SPC4955 aims to inhibit the production and export of LDL-C in the liver while our other clinical candidate SPC5001, increases the clearance of LDL from the blood. Working on two distinct compounds with different target pathways allows the company to address the broad spectrum of patients trying to control their high cholesterol levels.” 

In addition to its cardiometabolic programmes, in September 2010, Santaris Pharma A/S successfully advanced miravirsen, a lead microRNA drug candidate targeting miR-122, into phase II studies for the treatment of patients infected with the Hepatitis C virus. 

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders.

With its partners, Santaris Pharma A/S also has a robust product pipeline consisting of mRNA and microRNA drug discovery and development collaborations. These include partnerships with Pfizer, Inc. (delivery of lead candidates against up to 20 targets), miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), GlaxoSmithKline (four viral disease drug candidates) and Enzon Pharmaceuticals (eight cancer targets successfully delivered – three are now in phase I clinical studies).

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA-based drugs are a promising new class of therapeutics that are enabling scientists to develop drug candidates to work through previously inaccessible clinical pathways.

The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles.

The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favourable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles. 

Santaris Pharma A/S is a privately held clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states.

Source: Pharmabiz

Cell Biosciences receives three US patents

 Cell Biosciences, Inc. announced the issuance of three key patents by the United States Patent and Trademark Office, Patent Nos. 7,935,489, 7,935,308 and 7,935,479.

These patents address central aspects of Cell Biosciences' NanoPro Assay Technology. NanoPro assay systems utilize novel approaches to protein capture and detection to enable high-sensitivity measurement of specific proteins in complex biological samples. These patents each focus on the fundamental capture and detection methodologies at the core of NanoPro Assay Technology.

“We are extremely pleased by the issuance of these key patents,” commented Bob Gavin, vice president of Product Development at Cell Biosciences. “As we expand the NanoPro product line into new markets, a strong intellectual property position will become increasingly important.” 

Cell Biosciences is a private life sciences company focused on defining the future of protein analysis. The company develops instrumentation systems, software and assay products that help researchers better understand proteins for fundamental research, biotherapeutics production, biomarker discovery and personalized medicine.

Source: Pharmabiz

Thursday, May 12, 2011

New Technology Fuses MRI, Ultrasound to Achieve Targeted Biopsy of Prostate Cancer

 Targeted biopsy, a major advance in prostate cancer diagnostics, was detailed by a UCLA team in the current issue ofUrologic Oncology. The new technology fuses MRI with real-time 3D ultrasound, providing an exacting method to obtain biopsy specimens from suspicious areas in the prostate.

The unique fusion method provides a major improvement in the way prostate biopsy is performed since the current biopsy methods were developed in the mid-1980s, according to UCLA professor of urology Dr. Leonard S. Marks, a study author.

Four UCLA departments -- urology, radiology, pathology and biomedical engineering -- collaborated with the medical device company Eigen Inc. to develop and test the technology. The team's early experiences with it are reported in the online May/June issue of the journal Urologic Oncology.

"It's difficult to identify and target suspicious areas using two-dimensional, conventional ultrasound, so urologists currently take samples systematically from the entire prostate," said Marks. "The advent of MRI-ultrasound fusion has led to a promising advance in prostate imaging and biopsy targeting.

"Despite the technology revolution of the past several decades, we are still performing prostate biopsies just the same as in the mid-1980s," he said. "We are hopeful that new imaging methods like MRI-ultrasound fusion may soon change that."

According to the American Cancer Society, 230,000 cases of prostate cancer will be diagnosed this year, but not every one of them is deadly. Many small prostate cancers are not serious health threats, and in those cases, surveillance programs can help men avoid radical treatments like surgery. Many smaller cancers grow so slowly that they may never require treatment at all. The new imaging technology could help doctors differentiate the serious cancers from the insignificant.

Marks noted that the new technology may be most beneficial for patients who fall into one of two categories: those who had prior negative biopsies but have persistently elevated prostate-specific antigen (PSA) levels, and "active surveillance" patients -- those with low-risk prostate cancers who are being carefully monitored over time to see if their cancer progresses or becomes more aggressive.

The study, conducted between 2009 and 2010, involved 218 men between the ages of 35 and 87, all of whom received prostate biopsies. Of the 218, 47 men who fell into one of the two categories mentioned above received prostate biopsies using MRI images fused with real-time ultrasound. These patients first received MRI scans of the prostate that assessed three components in detecting cancer: suspicious contrasts in tissue, abnormal cellular density and unusual blood flow within the prostate.

"While other major cancers can be imaged within the organ of origin, the small, compact prostate has proven elusive for a number of reasons, such as the similarity of cancer and benign tissue and the lack of tissue uniformity," said study author Dr. Daniel Margolis, an assistant professor of radiology in abdominal imaging and co-director of prostate imaging at the David Geffen School of Medicine at UCLA. "We hope the multi-parameter MRI information, used with the new system, will help us better distinguish problem areas and provide the most accurate information possible."

After reviewing the MRI prostate scans, Margolis individually graded each component and provided an overall score to gauge cancer risk. He notes that the additional MRI information may help improve targeting and possibly eliminate the need for taking multiple biopsy samples. Currently, 12 areas from the entire prostate are systematically biopsied, whether they are suspicious areas or not.

For the next step, UCLA biomedical engineer Shyam Natarajan took the data and scores from the MRI prostate scans and, using software created at UCLA, generated a 3-D image of the 47 patients' prostates, which clearly showed the location of any suspicious areas. The information was transferred to a CD that was ready for use in the clinic during a real-time ultrasound prostate biopsy.

During the prostate biopsy, the CD was loaded into Artemis, a 3-D prostate biopsy system that allows the stored MRI images to be electronically transferred and fused with the real-time ultrasound, providing a 3-D image similar to a roadmap to help guide the tiny biopsy needle into targeted areas.

"The application of such three-dimensional imaging or modeling is used in other fields, like animation and gaming, and is also being used more frequently in developing medical diagnostics," said Natarajan, an author of the study and a researcher at both the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA Center for Advanced Surgical and Interventional Technology.

The other 171 men in the study did not undergo MRI but received prostate biopsies in which the Artemis tracking system was attached to the ultrasound probe, allowing their prostates to be scanned using 3-D imaging, which may be beneficial in providing more even distribution of the biopsy sites when using conventional ultrasound technology, according to the study authors.

The UCLA team found that targeted biopsy was about five times more likely to find cancer than non-targeted, systematic biopsy. Re-biopsy of a suspicious site was found to be accurate within a few millimeters.

"These early results are promising, but more study needs to be completed before we can conclusively show the benefit of tracking and targeting biopsy with this new method," said Marks.

The team is also helping track the accuracy of MRI-ultrasound fusion by studying cancerous prostates that have been removed from study patients. The researchers can then compare the location of the diseased tissue on the actual prostate with the MRI and ultrasound fusion scans.

"Using the actual prostate tissue allows us to pinpoint the exact location of the cancer, as well as assess the cancer's nature, such as determining if it will spread," said study author Dr. Jiaoti Huang, a professor and director of urologic pathology in the department of pathology at the Geffen School of Medicine. "We can also gauge the accuracy of the MRI and ultrasound fusion scans in identifying cancer."

The study was funded by grants from the Beckman Coulter Foundation, the Gordon Family Foundation and the Denney Foundation.

Eigen, a medical device company based in Grass Valley, Calif., manufacturers the Artemis device. The device was approved by the Food and Drug Administration in May 2008, but widespread distribution of it has been postponed until further usability development, like that underway at UCLA, has been achieved.

Additional study authors include Maria Luz Macairan and Patricia Lieu of the department of urology at the David Geffen School of Medicine at UCLA and Aaron Fenster, Ph.D., of the Robarts Research Institute at Canada's University of Western Ontario

Source: ScienceDaily

Botox Injected in Head ‘trigger Point’ Shown to Reduce Migraine Crises

 Scientists at the University of Granada have confirmed that injecting a local anesthetic or botulinum toxin (botox) into certain points named "trigger points" of the pericraneal and neck muscles reduce migraine frequency among migraine sufferers. University of Granada researchers have identified the location of these trigger points -which activation results in migraine- and their relationship with the duration and severity of this condition.

Headache is a universal experience. At present, there are more than 100 different types of headache and one of the most recurring ones is migraine, which affects approximately 10-12% of the population, being three times more common in women than in men. When migraine becomes chronic -occurring more than 15 days a month-, it can disrupt patients' daily life in a great degree.

This research study is one of the three studies that have been conducted by Juan Miguel García Leiva -a researcher at the University of Granada Institute for Neuroscience "Federico Oloriz" -- and coordinated by professor Elena Pita Calandre.

Trigger Points in Migraine Sufferers

In the first study, researchers examined a sample of healthy subjects and patients with a diagnosis of migraine -any frequency-, and analysed the presence of trigger points and their location, many of the explorations resulting in a migraine crisis. The most interesting findings of this study were: 95% of migraine sufferers have trigger points, while only 25% of healty subjects have them. The most common locations of trigger points are the anterior temporal and the suboccipital region, both billateral, of the head. Furthermore, researchers found a positive correlation among the number of trigger points in a patient, the number of monthly crises and the duration in years of the condition.

Subsequently, researchers conducted another study with 52 migraine sufferers (with migraine refractory to common pharmacological treatments). During three months, patients received a weekly subcutaneous injection of 1mL of a local anesthetic into their trigger points.

After the injection of the anesthetic, 18% of patients experienced a 50% or higher reduction in the frequency of migraine crises, as compared with the basal period. Additionally, an 11-49% reduction of frequency was observed in 38% of patients. Two thirds of the patients treated reported to feel "better or much better."

Few Side Effects

In the third study, 25 patients with chronic migraine were injected with 12.5 doses of botox into each trigger point twice, during a period of 3 months. Frequency (main variable), intensity and scales of migraine crises were recorded one month before and one month after the treatment to compare the changes experienced. In addition, side effects were also recorded during the experiment, and they were found to be mild and temporary.

After the injections, the most significant decrease in crisis frequency was observed at week 20. Similar results were obtained in those crises labelled as "moderate" and in the frequency of analgesic use by patients.

García Leiva specified that this treatment "is not a first-choice treatment for migraine sufferers, but it can only be applied in patients with chronic migraine who have tried several treatments with poor results, and who show peripheral sensitization of muscles. Recently, the Foods and Drugs Administration (USA) has approved botulinum toxin as a therapeutical drug for the treatment of chronic migraine.

Source: Science Daily

Scientists Use Genetically Altered Virus to Get Tumors to Tattle on Themselves

 Scientists have used a genetically re-engineered herpes virus that selectively hunts down and infects cancerous tumors and then delivers genetic material that prompts cancers to secrete a biomarker and reveal their presence.

 

According to a study appearing May 11 in PLoS ONE, published by the Public Library of Science, the novel technology has the potential to vastly improve cancer diagnosis by allowing the disease to be caught at much earlier stages and to monitor the effectiveness of therapy.

Researchers at Cincinnati Children's Hospital Medical Center who conducted the study say the new technique -- developed in preclinical mouse models -- could also be more cost effective and portable than current scanning technologies. This would make it useful for diagnosing cancers in less developed parts of the world.

"Our study represents a proof-of-principle in mice, and there is certainly room for further refinement. If ultimately validated in human trials, it could have implications for people with known cancer risk or who have a history of cancer and high risk of recurrence,'' said Timothy Cripe, M.D., Ph.D., senior investigator on the study and a physician and researcher in the Division of Oncology at Cincinnati Children's.

"Early cancer detection is vital to improve cure rates because cancer stage predicts prognosis, but biomarkers are known for only a few cancer types. We were able to use a reprogrammed herpes virus administered intravenously to deliver genetic information that induces a known blood biomarker for cancer to be secreted by cancer cells," explained Dr. Cripe, who collaborated on the study with first author, Andrew Browne, Ph.D., a fourth-year medical student at the University of Cincinnati (UC) College of Medicine and a recent graduate from UC's Department of Electrical and Computer Engineering.

The researchers engineered a herpes simplex virus mutant they called rQ-M38G, reprogramming its genetic makeup so it bypasses healthy tissues and instead targets rapidly dividing cancer cells for infection. They also genetically armed the virus so it prompts cancer cells to secrete Gaussia luciferase (GLuc).

GLuc is a luminescent, easily detectable protein the researchers used as a universal blood biomarker for cancer cells infected by rQ-M38G. Because rQ-M38G/GLuc might also help shrink cancer, it is part of a new class of agents dubbed "theragnostics" that can simultaneously be used for diagnosis and therapy, Dr. Cripe said.

Initially the researchers tested rQ-M38G on laboratory cell cultures of healthy dormant human skin cells and on rapidly dividing cancer cells. Virus replication and biomarker production were very low in the dormant normal cells. In contrast, virus replication and biomarker production were much higher in tumor cell lines of malignant peripheral nerve sheath tumors, osteosarcoma (bone cancer), rhabdomyosarcoma (muscle cancer) and Ewing sarcoma.

Researchers then tested the virus's detection capabilities in mouse models of these same cancers by injecting rQ-M38G into their tail veins, and for comparison into the tail veins of healthy control mice. Non-tumor bearing mice showed background signals for the virus without significant replications or biomarker production. More than 90 percent of the tumor bearing mice showed significant virus replication and biomarker production.

The technology even worked in some mice with only microscopic amounts of cancer in their kidneys, researchers report. If it were to work as well in humans, the scientists estimate that hidden tumors less than half-inch in diameter might be detectable. Because of the anticipated immune response against the virus and the GLuc protein in humans, further refinements of the technology will likely be needed to be able to use it more than once.

The study is one more example of the expanding research into using reprogrammed HSV as novel methods to treat or diagnose cancer, especially as medicine reaches the limits of modern chemotherapies. Dr. Cripe said this creates an urgent need for new strategies against stubborn metastatic disease. Less than 30 percent of patients with metastatic cancer survive beyond five years, despite the aggressive use of modern combination therapies that include chemotherapy.

Also collaborating on the current study were Jennifer Leddon, Mark Currier, Jon Williams, Jason Frischer, and Margaret Collins all of Cincinnati Children's.

Funding support for the study came from the CancerFree Kids Pediatric Cancer Research Alliance and the National Institutes of Health.

Source: ScienceDaily

 

Sanofi Pasteur launches Pentaxim, first 5-in-1 combination vaccine in China

 

Sanofi Pasteur, the vaccines division of Sanofi launched Pentaxim, the first 5-in-1 combination vaccine in China to immunize against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b. The debut of the first 5-in-1 combination vaccine was celebrated with over 200 Chinese and international experts and hailed as the beginning of a new era in the immunization field in China. In order to facilitate the adoption of the new combination vaccine for the benefit of consumers, the Chinese Preventive Medicine Association (CPMA) introduced a first-of-its-kind technical guideline for doctors at Points of Vaccination.

Pentaxim (DTaP-IPV-Hib) vaccine was first marketed in 1997. To date, more than 100 million doses of Pentaxim have been distributed in over 100 countries, and the vaccine has been included in the national immunization programs in 23 countries. Pentaxim vaccine is the first acellular pertussis pentavalent vaccine in China against five deadly childhood diseases. It reduces the number of shots from twelve to four, and achieves the same level of protection as immunized with single-antigen vaccines.

The launch of Pentaxim vaccine comes just eighteen months after Sanofi Pasteur introduced the first and only Inactivated Poliomyelitis Vaccine (IPV) to China. It also adds to a long list of innovative vaccines that Sanofi Pasteur has brought to the country, including the first rabies vaccine, the first influenza vaccine and the first Hib vaccine.

Presiding over the launch ceremony, Christopher A. Viehbacher, chief executive officer of Sanofi, said: “We are truly excited and proud to bring the first 5-in-1 combination vaccine to China, and we are greatly encouraged by the confidence and support of immunization experts in China. Over a century after Louis Pasteur invented the world’s first rabies vaccine, Sanofi Pasteur remains committed to its vision which is a world in which no one suffers or dies from a vaccine-preventable disease.”

Experts pointed out that, in addition to less shots for infants and greater comfort for parents, the new 5-in-1 (DTaP-IPV-Hib) combination vaccine ensures better compliance with the vaccination schedule. Fewer shots also mean time saved for parents and more efficiency at points of vaccination.

Professor Shen Xuzhuang from Beijing Children’s Hospital commented, “The launch of the first 5-in-1 combination vaccine supports the shared commitment of the Chinese government and the scientific community to enhance preventive healthcare. Vaccination remains the only effective way to prevent infectious diseases, and combination vaccines are clearly the future trend of vaccine development because of greater convenience, comfort and safety.”

 Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, rare diseases, consumer healthcare, emerging markets and animal health.

 

Source: Pharmabiz

Abbott's Humira meets primary endpoints in phase III ulcerative colitis study

 Abbott's Humira (adalimumab) met its primary endpoint of clinical remission in a phase III study of adult patients with moderate to severe ulcerative colitis. Results were presented at the Digestive Disease Week (DDW) scientific conference in Chicago.

Ulcerative Colitis (UC) is a chronic autoimmune disease that causes inflammation and ulceration in the lining of the colon or large intestine. It is estimated that approximately 700,000 people in the United States have UC. Symptoms include abdominal cramping, rectal bleeding, increased bowel movements and diarrhoea.

“There is an unmet need for patients living with ulcerative colitis,” said William J Sandborn, MD, division chief, Gastroenterology, University of California, San Diego and primary investigator for the study. “Unmanaged disease lends itself to painful symptom flares that can negatively impact patients, so the potential for new treatments is important for people managing this condition.”

The study analysis included 494 adult patients with UC who had not responded well to conventional therapy, such as corticosteroids and/or immunosuppressants. Patients were randomized 1:1 to placebo or Humira (160 mg, week 0; 80 mg, week 2; 40 mg every other week starting at week 4). Co-primary endpoints were the proportion of patients with clinical remission at week 8 and clinical remission at week 52. Clinical remission was defined as a Mayo Score of 2 or less with no individual subscore greater than 1. The Mayo Score uses a 12-point scoring system to measure disease activity which is evaluated by scoring the following parameters: stool frequency, rectal bleeding, endoscopy findings and physicians global assessment. A higher Mayo Score indicates greater disease severity.

Of the 248 patients treated with Humira in the study, 16.5 percent achieved clinical remission compared to 9.3 percent on placebo at week 8 p=0.019). At week 52, 17.3 percent achieved clinical remission compared to 8.5 percent on placebo (p=0.004).  These results were statistically significant compared to placebo.

The safety results were consistent with the known safety profile of Humira. Incidence of injection site reaction-related adverse events and hematologic adverse events were greater in Humira-treated patients compared to placebo-treated patients.

“People living with ulcerative colitis currently have very few treatment options to help them manage their disease,” said Eugene Sun, MD, vice president, Global Pharmaceutical Clinical Development, Abbott. “We are encouraged by these study results with Humira and the potential they may have for patients.”

Humira is not approved for the treatment of UC. Abbott recently submitted applications to both the US Food and Drug Administration and the European Medicines Agency seeking approval to market Humira for the treatment of moderate to severe UC.

On average, people are diagnosed with ulcerative colitis in their mid-30s, though the disease can occur at any age. The symptoms of UC tend to come and go, with fairly long periods of remission between flare-ups. Common complications include bleeding, perforation of the bowel and abdominal distension. Treatment may include medication, restoring and maintaining proper nutrition, and surgery. During their lifetimes, approximately 25 percent of UC patients will undergo surgery to treat their symptoms.

Humira is a prescription medicine used alone, with methotrexate, or with certain other medicines to reduce the signs and symptoms of moderate to severe rheumatoid arthritis in adults, may prevent further damage to your bones and joints, and may help your ability to perform daily activities. It is used alone, with methotrexate, or with certain other medications to reduce the signs and symptoms of moderate to severe polyarticular juvenile idiopathic arthritis in children 4 years of age and older. It is used alone or with certain other medicines to reduce the signs and symptoms of psoriatic arthritis in adults, may prevent further damage to your bones and joints, and may help your ability to perform daily activities. It is used to reduce the signs and symptoms of ankylosing spondylitis in adults.

Humira is used to reduce signs and symptoms, and achieve and maintain clinical remission in adults with moderate to severe Crohn's disease who have not responded well to conventional treatments, and in these adults who have also lost response to or are unable to tolerate infliximab. It is used to treat adults with moderate to severe chronic plaque psoriasis who are ready for systemic therapy or phototherapy, and are under the care of a doctor who will decide if other systemic therapies are less appropriate.

Humira is a TNF blocker that affects the immune system and can lower the ability to fight infections. People treated with Humira are at an increased risk for developing serious infections that may lead to hospitalization or death. Reported serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. People should be tested for TB before Humira use and monitored for signs and symptoms of TB during therapy. People at risk of TB may be treated with medicine for TB. Treatment with Humira should not be started in a person with an active infection, unless approved by a doctor. Humira should be stopped if a person develops a serious infection.

For people taking TNF blockers, including Humira, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death.

Other possible serious side effects with Humira include hepatitis B infection in carriers of the virus, allergic reactions, nervous system problems, blood problems, certain immune reactions, including a lupus-like syndrome, liver problems, and new or worsening heart failure or psoriasis. The use of Humira with anakinra or abatacept is not recommended. People using Humira should not receive live vaccines.

Common side effects of Humira include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.

As with any treatment program, the benefits and risks of Humira should be carefully considered before starting therapy.

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics.

Source: Pharmabiz

Roche submits NDA in US and Europe for vemurafenib in advanced skin cancer

 Roche announced that the company submitted a New Drug Application for vemurafenib (RG7204, PLX4032) to the US Food and Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency (EMA) for approval for people with BRAF V600 mutation-positive metastatic melanoma. Roche also submitted an application for the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic. Vemurafenib, a “BRAF-inhibitor,” is designed to selectively target and inhibit a mutated form of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.

“We have worked swiftly to advance the vemurafenib development programme knowing that patients with metastatic melanoma have a poor prognosis and limited treatment options,” said Hal Barron M.D., chief medical officer and head, global product development. The regulatory submissions of vemurafenib and the companion diagnostic to identify people with the type of melanoma specifically targeted by this medicine are exciting steps toward our goal of delivering a personalized therapy for this disease.”

The submissions are based on results from two positive clinical studies (BRIM2 and BRIM3) that evaluated vemurafenib in people with BRAF V600 mutation-positive metastatic melanoma, as determined by the investigational companion diagnostic test also being developed by Roche. A Premarket Approval Application for the cobas 4800 BRAF V600 Mutation Test was submitted in the U.S. The test will also will also be registered in Europe.

When melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. A person with metastatic melanoma typically has on average a short life expectancy that is measured in months. Less than one in four people are expected to be alive one year after a diagnosis and every year there are an estimated 40,000 deaths worldwide from the disease.

The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Mutations that keep the BRAF protein in an active state may cause excessive signalling in the pathway, leading to uncontrolled cell growth. These mutations of the BRAF protein are thought to occur in an estimated half of all melanomas and eight percent of solid tumours.

BRIM3 is a global, randomised, open-label, controlled, multicentre, phase III study that compared vemurafenib to dacarbazine chemotherapy, a current standard of care, in 675 patients with previously untreated BRAF V600 mutation-positive, unresected or locally advanced metastatic melanoma. The study met its two co-primary endpoints and showed that participants who received vemurafenib lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival) compared to those who received dacarbazine chemotherapy. The safety profile was consistent with previous vemurafenib studies.

Full data from BRIM3 will be presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 5, 2011 in Chicago.

BRIM2 is a global, single-arm, multicentre, open-label Phase II study that enrolled 132 patients with previously treated BRAF V600 mutation-positive metastatic melanoma. The primary endpoint of the study was overall response rate as assessed by an independent review committee. The study showed that vemurafenib shrank tumours in 52 percent of trial participants. People who participated in the trial lived a median of 6.2 months without their disease getting worse (median PFS). Updated data from BRIM2 will also be presented at the ASCO Annual Meeting.

The most frequent Grade 3 adverse event observed in clinical trials of vemurafenib was cutaneous squamous cell carcinoma, a common skin cancer treated by local excision (minor surgery done in a physician’s office). The most common adverse events were rash, photosensitivity, joint pain, hair loss and fatigue.

Vemurafenib (pronounced vem oo RAF en ib) is an investigational, oral, small molecule that is designed to selectively inhibit a cancer-driving mutated form of the BRAF protein. Vemurafenib is being co-developed under a 2006 license and collaboration agreement between Roche/Genentech and Plexxikon. The cobas 4800 BRAF V600 Mutation Test is an investigational, polymerase chain reaction-based companion diagnostic being developed by Roche to identify people whose tumours carry the BRAF V600 mutation.

Roche is considering a broad development program with vemurafenib that may include combinations with other medicines (both approved and investigational, from Roche and other companies), as well as studies in other tumour types. While Roche seeks approval of the drug, vemurafenib is available to eligible patients with BRAF V600 mutation-positive metastatic melanoma through a global patient access programme. 

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS

Source: Pharmabiz

Phylogica & Pepscan enter collaboration to optimise therapeutic Phylomer drug candidates

 

Phylogica Ltd, a leading Australian peptide drug discovery company, and Pepscan Therapeutics, a Dutch biopharmaceutical firm focusing on protein mimicry technology, announced that they have entered a Research Collaboration and Option Agreement to evaluate the combination of their complementary peptide technologies for drug discovery. 

Under the terms of the agreement, Pepscan using its CLIPS technology will work with Phylogica to optimise novel therapeutic Phylomer drug candidates against CD40-ligand for the treatment of rheumatoid arthritis, autoimmune diseases and inflammatory disorders. Phylogica will also have an option to expand the collaboration to include an undisclosed number of other disease-associated targets. Financial details were not disclosed.

Phylogica’s CEO, Dr Paul Watt, said: "We are excited to be working with Pepscan, which has world-class technology for improving the activity and stability of therapeutic peptides. We strongly believe that the combination of Pepscan’s CLIPS technology with our potent Phylomer peptides will further enhance our ability to generate breakthrough drug candidates against difficult-to-treat diseases.”

Dr Wim Mol, CEO of Pepscan, said: "We jointly recognise the perfect match of our combined technologies - Phylogica providing truly innovative peptide leads, and Pepscan applying its state-of-the-art CLIPS technology for peptide lead optimisation. We therefore believe that this agreement only forms the start of a promising and productive relationship between our two companies”.

Phylomer peptides are derived from biodiverse natural sequences, which have been selected by evolution to form stable structures, which can bind tightly, and specifically to disease associated target proteins, both inside and outside cells. Suitable targets for blockade by Phylomers include protein interactions that promote multiple diseases, such as infectious diseases, cancer, autoimmunity and heart disease. Phylomer peptides can have drug-like properties, including specificity, potency and thermal stability, and are capable of being produced by synthetic or recombinant manufacturing processes. Phylomer peptides are also readily formulated for administration by a number of means, including parenteral or intranasal delivery approaches.

CLIPS (Chemical LInkage of Peptides onto Scaffolds) is a technology to present one or more peptides in a structurally constrained configuration. These molecules behave as functional mimics of structurally complex protein domains. CLIPS therapeutic peptides have been shown to exert improved activity and stability. CLIPS peptides are also used as superior immunogens for antibody generation against disease relevant protein targets. This is especially valuable in the case of proteins that are inaccessible as recombinant proteins, such as GPCRs.

Phylogica Limited is a biotechnology company based in Perth, Australia, and Oxford, UK, with a world-class drug discovery platform harnessing the rich biodiversity of nature to discover novel peptide therapeutics. The company was incorporated in 2001 as a spin out from the Telethon Institute for Child Health Research (Perth, Australia) and the Fox Chase Cancer Centre (Philadelphia, USA). 

Pepscan Therapeutics is a privately held biopharmaceutical company based in Lelystad, The Netherlands. Pepscan is applying its proprietary high throughput CLIPS protein mimicking technology for the development of novel constrained therapeutic peptides and immunogens.

 

Source: Pharmabiz

Wednesday, May 11, 2011

Health-Care Providers Are Prescribing Nontraditional Medicine: Use of Mind-Body Therapies on the Rise

 More than a third of Americans use some form of complementary and alternative medicine (CAM) and that number continues to rise attributed mostly to increases in the use of mind-body therapies (MBT) like yoga, meditation and deep breathing exercises.

Prior research suggests that MBT, while used by millions of patients, is still on the fringe of mainstream medical care in America. New research suggests that attitudes are changing.

In a study from Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, researchers found that one in 30 Americans using MBT has been referred by a medical provider.

"There's good evidence to support using mind-body therapies clinically," said lead author Aditi Nerurkar, MD, Integrative Medicine Fellow, Harvard Medical School and BIDMC. "Still, we didn't expect to see provider referral rates that were quite so high."

The results of the study appear in the May 9 issue of theArchives of Internal Medicine.

Nerurkar and her colleagues collected information from more than 23,000 U.S. households from the 2007 National Health Interview Survey. They found that nearly 3 percent (representing more than 6.3 million Americans) used MBT due to provider referral and that these Americans were sicker and used the health care system more than people who self-referred for MBT.

"What we learned suggests that providers are referring their patients for mind-body therapies as a last resort once conventional therapeutic options have failed. It makes us wonder whether referring patients for these therapies earlier in the treatment process could lead to less use of the health care system, and possibly, better outcomes for these patients," said Nerurkar.

"These data suggest that mind-body therapies have really become a mainstream approach to care," adds Russell Phillips, MD, Chief of Primary Care at BIDMC and the senior author on the study. "But more research is needed to guide physician and patient decision-making regarding their use."

Source: ScienceDaily

Low Vitamin D in Kids May Play a Role in Anemia

 Pediatricians from Johns Hopkins Children's Center and elsewhere have discovered a link between low levels of vitamin D and anemia in children.

The findings, presented May 1 at the annual meeting of the Pediatric Academic Societies in Denver, Colo., show that vitamin D deficiency may play an important role in anemia.

Anemia, which occurs when the body has too few oxygen-carrying red blood cells, is diagnosed and tracked by measuring hemoglobin levels. Symptoms of mild anemia include fatigue, lightheadedness and low energy. Severe and prolonged anemia can damage vital organs by depriving them of oxygen.

To examine the relationship between hemoglobin and vitamin D, the researchers looked at data from the blood samples of more than 9,400 children, 2 to 18 years of age. The lower the vitamin D levels, the lower the hemoglobin and the higher the risk for anemia, the researchers found. Children with levels below 20 nanograms per milliliter (ng/ml) of blood had a 50 percent higher risk for anemia than children with levels 20 ng/ml and above. For each 1 ng/ml increase in vitamin D, anemia risk dropped by 3 percent.

Only 1 percent of white children had anemia, compared with 9 percent of black children. Black children also had, on average, much lower vitamin D levels (18) than white children (27). Researchers have long known that anemia is more common in black children, but the reasons for this remain unclear, although some suspect that biologic and genetic factors may be at play.

The new findings, however, suggest that low vitamin D levels in black children may be an important contributor to anemia.

"The striking difference between black and white children in vitamin D levels and hemoglobin gives us an interesting clue that definitely calls for a further study," said lead investigator Meredith Atkinson, M.D., M.H.S., a pediatric nephrologist at the Johns Hopkins Children's Center.

While the findings show a clear link between low vitamin D levels and anemia, they do not prove that vitamin D deficiency causes anemia, the investigators caution.

Source: ScienceDaily

Scientists Discover Way to Amp Up Power of Killer T Cells to Fight Melanoma

 Researchers with UCLA's Jonsson Comprehensive Cancer Center have discovered a way to amp up the power of killer T-cells, called CD8 cells, making them more functional for longer periods of time and boosting their ability to multiply and expand within the body to fight melanoma, a new study has found.

The study, done in mouse models of metastatic melanoma that had spread to the brain, has important clinical implications, as the method could boost the cancer-killing power of experimental immunotherapies being tested now in various cancers, including deadly glioblastoma and metastatic melanoma, both of which are very difficult to treat successfully.

Study senior author Dr. Robert Prins, an associate professor of neurosurgery and a Jonsson Cancer Center scientist, said the killer T cells also were better able to recognize and traffic to the cancer, which is crucial as the immune system often fails to identify malignant cells as invading enemies.

The study is published in the May issue of the peer-reviewed the Journal of Immunology.

The process Prins and his team used sought to mimic the way the T cells in the immune system recognize and fight viruses in the body, stimulating what is called the innate immune system. The innate immune system is composed of cells that immediately defend the body from infection and frequently is not stimulated in the presence of cancer, Prins said. However, the innate immune cells can be tricked into thinking a virus is present by treating with compounds that activate Toll-like receptors (TLR).

Prins' group had previously demonstrated that TLR agonists, such as imiquimod, could synergize with dendritic cell vaccines, both in mouse models and patient clinical trials. Interleukin 12 (IL-12) is one of the predominant cytokines released when TLR are activated. In this study, they wanted to see how IL-12 would affect the CD8 T cells.

Graduate student Dominique Lisiero, first author of the study, said CD8 T cells come in a large variety of "flavors" and can be stimulated in differing ways. However, what signals and which stimuli work best to prime the cells to fight cancer was unclear. Lisiero added IL-12 to the CD8 T cells in culture, before the cells were transferred into mice with established brain tumors.

"We wanted to see if we could make these cells become better at either recognizing the tumor or killing tumor cells," she said. "We didn't know what expect, but what we found was that when we programmed these cells in the presence of IL-12, we saw that the tumors decreased in size and the mice with brain metastases survived longer. In fact, Prins said that the mice treated with killer T cells primed in the presence of IL-12 lived about 2.5 times longer than those not receiving the IL-12.

To better understand the mechanisms by which priming killer T cells in the presence of IL-12 really enhanced their function, the team focused on how these T cells responded to a different cytokine, Interleukin 2 (IL-2). IL-2, which is instrumental for the body's natural response to infection and recognition of foreign invaders, often is included in adoptive transfer immunotherapies to help the T cells survive, but it has to be given in high doses that frequently cause significant toxicity to patients. Prins and Lisiero wanted to know if adding IL-12 would enhance the sensitivity of IL-2 signaling inside the T cells.

"T cells that were primed in the presence of IL-12 had a higher expression of the IL-2 receptor, meaning the T cells had an enhanced ability to respond to the IL-2. This, we believe, allowed the killer T cells to expand and survive after being transferred into mice with brain tumors. " Lisiero said. "Because the IL-12 stimulates the IL-2 receptor, we can give much lower doses of IL-2 and still get the same anti-tumor function from the killer T cells. In patients, this may translate to reduced toxicity. Clinical trials, however, would be required to prove that this priming with IL-12 would have similar effects."

Lisiero also tested the new process on human T cells, culturing them in either IL-2 or IL-12, and studying their function in the lab. The function of the cells programmed in IL-12 was dramatically increased, Prins said, validating the work in the mouse models. Their findings are already influencing how T cells are grown in the lab, he said.

The findings also are translational to the clinic, since metastatic melanoma patients in clinical trials often are removed from the protocol when the cancer appears in their brain. Many oncologists and scientists still believe that T cells can't access the brain because of its immune privilege. This study, however, has proven in a pre-clinical model that these tumors in the brain can in fact be effectively targeted.

"The in vitro priming of mouse tumor-specific CD8 T cells in the presence of IL-12 induced a diverse and rapid anti-tumor effector activity while still promoting the generation of memory cells," the study states. "Importantly, the IL-12-primed effector T cells dramatically reduced the growth of well-established tumors and significantly increased survival to highly immune resistant, established intracranial tumors."

 

Source: ScienceDaily

US FDA approves Sanofi Pasteur’s Fluzone Intradermal vaccine

 Sanofi Pasteur, the vaccines division of Sanofi announced the US Food and Drug Administration (FDA) has approved the company’s supplemental Biologics License Application (sBLA) for licensure of Fluzone Intradermal (Influenza Virus Vaccine). Fluzone Intradermal vaccine is indicated for active immunization of adults 18 through 64 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

“The micro-injection delivery system utilized in Fluzone Intradermal vaccine provides reliable and easy delivery of the vaccine into the dermal layer of the skin, an attractive site for immunization,” said Olivier Charmeil, president and CEO, Sanofi Pasteur. “Sanofi Pasteur is proud to bring this innovation in influenza vaccine administration to the US, offering health-care providers a new tool that may help enhance adult influenza immunization rates.”

The new formulation of Fluzone Intradermal vaccine is the first influenza vaccine licensed in the US that uses a novel micro-injection system for intradermal delivery. Fluzone Intradermal vaccine features an ultra-fine needle that is 90 percent shorter than the typical needle used for intramuscular injection of influenza vaccine. Sanofi Pasteur has previously licensed micro-injection intradermal influenza vaccines, marketed as Intanza or IDflu vaccines, in more than 40 countries including Australia, Canada and countries in Europe.

Fluzone Intradermal vaccine incorporates a new, easy-to-use, pre-filled micro-injection system designed to consistently deposit vaccine antigens into the dermal layer of the skin of adults. The dermal layer contains a high concentration of specialized cells known as dendritic cells, which play a key role in generating an immune response. In clinical trials, Fluzone Intradermal vaccine produced an immune response at rates similar to Fluzone vaccine administered intramuscularly.

Typically, adult influenza vaccines are administered into the muscle utilizing a needle 1 inch to 1.5 inches (25 mm to 38 mm) in length. Fluzone Intradermal vaccine features an ultra-fine needle that is 0.06 inches (1.5 mm) in length. Fluzone vaccine contains 15 mcg of hemagglutinin per strain of influenza in a 0.5 mL dose. Fluzone Intradermal vaccine contains 9 mcg of hemagglutinin per strain of influenza in a 0.1 mL dose.

Fluzone Intradermal vaccine will be available to health-care providers in the US for the 2011-2012 influenza season.

Clinical trials were conducted to evaluate the safety and immunogenicity of Fluzone Intradermal vaccine. Fluzone Intradermal vaccine was licensed based on data from a phase III clinical trial in 4,276 adults 18 years through 64 years of age (2,855 participants received Fluzone Intradermal vaccine and 1,421 participants received Fluzone vaccine via intramuscular administration). The study, which assessed the safety and immunogenicity of Fluzone Intradermal vaccine in comparison to Fluzone vaccine, was presented in October 2010 at the 48th Annual Meeting of the Infectious Diseases Society of America in Vancouver, British Columbia. In the phase III trial, Fluzone Intradermal vaccine was found to induce immunologic responses similar to licensed Fluzone vaccine.

Systemic reactogenicity of Fluzone Intradermal vaccine was comparable to that of intramuscular administration of Fluzone vaccine in the study. Intradermal micro-injection deposits influenza vaccine near the surface of the skin; therefore, local reactions are more easily visible. The most common solicited injection-site reactions reported in participants given the intradermal vaccine were erythema (redness) (>75%), swelling (>50%), induration (hardness) (>50%), pain (>50%) and pruritus (itching) (>40%). The injection-site and systemic reactions with intradermal administration were transient, resolving in three to seven days without sequelae. The injection-site reactions were more frequent with participants given the intradermal vaccine compared to the intramuscular vaccine, with the exception of pain, which was similar.

Influenza is a serious respiratory illness that is easily spread and can lead to severe complications, even death. Each year in the US, 5 to 20 percent of the population gets the flu and an estimated 226,000 people are hospitalized from flu-related complications. Flu seasons are unpredictable and can be severe. Depending on virus severity during the influenza season, annual deaths can range from a low of 3,000 to a high of about 49,000 people. Combined with pneumonia, influenza is the nation’s eighth leading cause of death. Vaccination is safe and effective and the best way to help prevent influenza and its complications.

The Centres for Disease Control and Prevention recommends annual influenza vaccination for everyone 6 months of age and older to help protect against influenza and its complications. Adults younger than 65 years of age are among those with the lowest rates of immunization against influenza. Fluzone Intradermal vaccine, which is licensed for adults 18 through 64 years of age, is anticipated to provide an attractive immunization option for this age group.

The most common local and systemic adverse reactions to Fluzone Intradermal vaccine include erythema (redness), induration (firmness), swelling, pain, and pruritus (itching) at the vaccination site; headache, myalgia (muscle ache), and malaise. Other adverse reactions may occur. Fluzone Intradermal vaccine should not be administered to anyone with a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or to a previous dose of any influenza vaccine. The decision to give Fluzone Intradermal vaccine should be based on the potential benefits and risks, especially if Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine. Vaccination with Fluzone Intradermal vaccine may not protect all individuals.

Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, rare diseases, consumer healthcare, emerging markets and animal health.

Source: Pharmabiz

Napo Pharma sues Salix over breach of collaboration agreement

 

Salix Pharmaceuticals, Ltd. announced that Napo Pharmaceuticals, Inc. has filed a lawsuit against Salix Pharmaceuticals alleging that the company has breached its commitments under the collaboration agreement between Napo and Salix concerning the development of crofelemer. 

According to company lawyers, Napo's claims are without merit and the lawsuit is baseless. Salix intends to vigorously defend against the lawsuit and plans to continue with the development and commercialization of crofelemer in accordance with its past guidance and the terms of its collaboration agreement with Napo. 

Salix Pharmaceuticals, Ltd., develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in–license late–stage or marketed proprietary therapeutic drugs, complete any required development and regulatory submission of these products, and market them through the company's gastroenterology specialty sales and marketing team. 

 

Source: Pharmabiz

Health economics sub-study of PLATO shows Brilique to be cost effective treatment versus generic clopidogrel

 AstraZeneca announced new health economics data from a sub-study of the PLATO trial showed that treating a broad spectrum of Acute Coronary Syndrome (ACS) patients with Brilique (ticagrelor) was more cost-effective than treatment with generic clopidogrel.

The study demonstrated that ticagrelor provided a cost-effective gain in Quality-Adjusted Life Year (QALY) compared to generic clopidogrel based on the approved ticagrelor label in the European Union (EU). Specifically, ACS patients treated with ticagrelor and aspirin, compared with generic clopidogrel plus aspirin for one year on average were projected to gain an additional 0.13 QALYs at a cost range of €2,350 ($3,110)–€5,700 ($7,550) per QALY. The PLATO trial (A Study of PLATelet Inhibition and Patient Outcomes) was the pivotal phase III study that formed the basis of the EU label.

Cost per QALY is an important measure used by national governments and their reimbursement agencies to assess cost effectiveness of medical treatments. While no universal threshold for cost effectiveness exists, generally, a cost per QALY in the range of €25,000 ($33,000) to €38,000 ($50,000) is considered cost effective.

“The PLATO health economics substudy accounts for both the clinical effect observed in PLATO as well as cost considerations for treating ACS patients with ticagrelor versus clopidogrel,” said Dr Lars Wallentin, director and Professor of Cardiology, Uppsala Clinical Research Centre & University Hospital, Sweden. “What is particularly impressive about this sub-study is that even at a higher price, ticagrelor was a cost effective treatment for ACS patients compared to generic clopidogrel.”

The price of generic clopidogrel €0.17 ($0.23) per day was compared with the price range of Brilique of €2.25 ($3.00) to €3.50 ($4.65) per day and applied in the analysis to form the price component of the health economics sub-study. Using individual patient data from PLATO and event rates, health care costs based on Swedish base-case analysis and QALYs were estimated for the first year. The analysis showed that the overall cost impact of using ticagrelor instead of clopidogrel was cost effective.

The analysis is now published in the May/June issue of the International Society for Pharmacoeconomics and Outcomes Research’s Value in Health and will be presented at the organisation’s international annual meeting on 23 May.

AstraZeneca also announced that ticagrelor has been accepted for reimbursement by the Scottish Medicines Consortium (SMC) for patients in Scotland. The Ministry of Health and Prevention in Denmark also recently approved ticagrelor as the first branded oral anti-platelet therapy to achieve national reimbursement for a broad ACS population.

Health technology assessments ongoing in the remainder of the UK and in Germany are expected later this year by NICE and IQWiG, respectively, however healthcare professionals are able to prescribe ticagrelor in accordance with local guidance. Markets where a price has been approved but the reimbursement process is ongoing include Finland, Norway, Portugal, and Austria.

“These new data help further demonstrate the compelling value proposition ticagrelor offers versus a widely used generic. We also welcome the positive decision in Scotland and Denmark to reimburse ticagrelor and believe it will become an attractive option for physicians seeking another antiplatelet treatment to reduce their ACS patients’ risk of heart attack and cardiovascular death,” said Tony Zook, executive vice president of AstraZeneca’s Global Commercial Organisation. “Further reimbursement processes are underway according to local rules and regulations and timings will differ from market to market. We will continue to work with the appropriate health organisations, formulary and protocol review boards, and clinicians to ensure patients have access to this important medicine as soon as possible.”

Brilinta is an oral anti-platelet treatment for Acute Coronary Syndromes (ACS). It is a direct-acting P2Y12 receptor antagonist in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs). It is the first reversibly-binding oral ADP receptor antagonist.

Brilinta is currently under regulatory review in 33 countries, including the United States. The product has been approved in 32 countries, including in the European Union, Iceland, and Norway under the trade name Brilique and in Brazil under the trade name Brilinta.

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease.

Source: Pharmabiz

Onyx Onyx Scientific clinches Cancer Research UK contract

 The UK’s leading cancer charity has awarded a major drug development and manufacturing project to chemistry experts Onyx Scientific.

Cancer Research UK has selected the UK-based Active Pharmaceutical Ingredient (API) manufacturer to develop the chemistry and perform the GMP synthesis of the API for use in a phase I clinical trial.

The team at Cancer Research UK initially approached its preferred suppliers with its requirements and a proposed development route. After analysing the charity’s needs in more detail, the technical team at Onyx Scientific has improved the synthetic methodology as well as suggesting an alternative route, which long term will potentially help make the project more efficient and cost effective.

Dr Nigel Westwood, drug supply manager at Cancer Research UK, said: “Having had a very positive experience of using Onyx Scientific’s process development and GMP manufacturing services in the past, they seemed like a strong candidate for this important project.”

“Despite the fact that Cancer Research UK had to change suppliers at such a critical stage, Onyx Scientific still expect to bring the project in on time and on budget. Given their expertise in chemistry and ability to deliver, we believe they are perfect fit for the project,” added Dr Westwood.

Onyx Scientific provides outsourced facilities and expertise to help pharmaceutical and biotech companies accelerate drug candidates from discovery, through development, into phase I/II GMP API manufacturing. The Cancer Research UK project is one of the biggest projects in the firm’s history and is expected to take around seven months to complete.

Denise Bowser, commercial director at Onyx Scientific, said: “We are delighted to be working again with the team at Cancer Research UK on this major project as it clearly indicates confidence in our technical expertise, customer service and ability to deliver on time.”

“The input we have had to date has been positive and has no doubt demonstrated our commitment to go the extra mile for clients by meeting their requirements as efficiently as possible” he added.

Onyx Scientific has worked on contract chemistry, development and production projects for over 150 organisations across the world. It now operates as a preferred partner of around half of the world’s top 10 big pharma firms and has achieved a 96% customer loyalty rate based on repeat projects.

Source: Pharmabiz

Astellas, Medivation initiate phase II trial of MDV3100 in hormone-naive prostate cancer patients

 Astellas Pharma Inc. and Medivation, Inc. announced treatment of the first patient in the second new phase II clinical trial of the investigational drug MDV3100, a triple-acting oral androgen receptor antagonist. This trial is evaluating MDV3100 monotherapy as the first hormonal treatment of patients with prostate cancer. Enrolled patients would not have had any previous hormonal therapies for the treatment of prostate cancer. This is the first trial to examine the effects of MDV3100 without a background of medical or surgical castration. 

“This is the second of two phase II trials that we and our partner Medivation have initiated this year to evaluate the potential benefit of MDV3100 in both advanced and earlier stage prostate cancer patients,” said Steven Ryder, MD, president, Astellas Pharma Global Development. “Investigating MDV3100 monotherapy is the next important step to potentially providing a new option for prostate cancer patients with earlier stage disease.”

The open-label, single-arm phase II trial is planned to enroll approximately 60 patients in Europe. The primary endpoint of the trial is Prostate-Specific Antigen (PSA) response. The trial will evaluate MDV3100 at a dose of 160 mg taken orally once daily for 24 weeks.

In addition to this trial, MDV3100 is currently being evaluated in the Terrain study, a phase II trial comparing MDV3100 with bicalutamide, a commonly used anti-androgen, in the treatment of advanced prostate cancer patients who have progressed while on LHRH analogue therapy or following surgical castration. Terrain is expected to enroll approximately 370 patients in North America and Europe. The primary endpoint of the trial is progression-free survival.

MDV3100 is also being evaluated in two global phase III studies in patients with advanced prostate cancer. 

The randomized, double-blind, placebo-controlled phase III AFFIRM trial completed enrollment in November 2010. This trial of 1,199 patients with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy is evaluating 160 mg/day of MDV3100 versus placebo. The primary endpoint is overall survival. 

A second phase III clinical trial of MDV3100 in advanced prostate cancer, the Prevail trial, is currently enrolling patients. This randomized, double-blind, placebo-controlled, multi-national trial of approximately 1,700 men with advanced prostate cancer who have not yet received chemotherapy is evaluating MDV3100 at a dose of 160 mg taken orally once daily plus standard of care versus placebo plus standard of care. The co-primary endpoints of the trial are overall survival and progression-free survival. Information about patient eligibility and enrollment can be obtained by calling the PREVAIL study hotline toll-free at 1-888-243-4363. 

MDV3100 is an investigational therapy in clinical development for advanced prostate cancer. In a phase I-II trial in 140 patients with advanced prostate cancer published in The Lancet, encouraging anti-tumour activity was noted with MDV3100 across endpoints. In preclinical experiments published in Science in April 2009, the triple-acting, oral androgen receptor antagonist provided more complete suppression of the androgen receptor pathway than bicalutamide, the most commonly used anti-androgen. It slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions and blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation) and inhibits binding to DNA. In the preclinical experiments published in Science, MDV3100 was superior to bicalutamide in each of these three actions. 

Prostate cancer is the second most common non-skin cancer among men in the world and the sixth leading cause of cancer death among men worldwide. Patients whose prostate tumours have stopped responding to, or are growing despite the use of, active hormone treatment strategies are considered to have advanced prostate cancer. These patients have a poor prognosis and few treatment options. 

In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize MDV3100. The companies are collaborating on a comprehensive development programme that includes studies to develop MDV3100 across the full spectrum of advanced prostate cancer disease states. Subject to receipt of regulatory approval, the companies will jointly commercialize MDV3100 in the US and Astellas will have responsibility for commercializing MDV3100 outside the US. Medivation received a $110 million up-front payment upon entering into the collaboration agreement, and is eligible to receive up to $335 million in development milestone payments, up to $320 million in commercial milestone payments, 50% of profits on sales in the US, and tiered, double-digit royalties on sales outside the United States. 

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases for which there are limited treatment options and aims to transform the treatment of these diseases and offer hope to critically ill patients and their caregivers.

Astellas Pharma Inc., is dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. The company is committed to becoming a global category leader in Urology, Immunology & Infectious Diseases, Neuroscience, DM complications & Metabolic Diseases and Oncology.

Source: Pharmabiz

Geron statement regarding European cancer vaccine patents

 Geron Corporation commented on a ruling from the European Patent Office (EPO) with regard to its European patent 084139, and the issuance of a second Geron patent covering telomerase peptides, EP1783139.

In a March 31 ruling, the EPO Technical Board of Appeal (TBA) upheld a 2006 decision by the EPO Opposition Division cancelling three of the 47 claims of EP 084139 and maintaining the other 44 claims in the patent. The cancelled claims covered the use of telomerase peptides in vaccines for treating cancer. The opposition was originally brought by Pharmexa A/S of Denmark, which was developing GV1001, a telomerase peptide cancer vaccine. The rights to GV1001 were subsequently acquired by KAEL-GemVax, which is now conducting a European phase III trial combining GV1001 with other agents to treat pancreatic cancer. An earlier phase III single agent study of GV1001 in pancreatic cancer was reported to have been halted after a preliminary analysis showed no survival benefit.

“We understood the basis for the decision of the Opposition Division in 2006 and indicated at that time that we would file a divisional patent application to secure equivalent claim coverage,” said David J Earp, JD, PhD, Geron's chief patent counsel and senior vice president of business development. “We have been successful in that strategy and have been awarded a second European patent, EP1783139. The claims in this second patent were drafted in view of the earlier Opposition Division decision and specifically focus on telomerase peptides. The claims of this second issued patent clearly cover commercial use of the GV1001 product. While this patent has also been opposed by KAEL-GemVax, we believe that the issued claims are robust and should be upheld.”

Geron holds worldwide exclusive patent rights for technologies enabled by the cloning of the telomerase gene, which was accomplished by a team of Geron scientists and Dr Tom Cech and his colleagues at the University of Colorado. In addition to the European patents, Geron holds rights to telomerase patents worldwide including the US, Japan, Australia, South Korea and China. Geron has two product candidates, GRNVAC1 and GRNVAC2, designed to generate immune responses to telomerase using nucleic acids delivered to dendritic cells. Patent claims covering these programs were upheld in the TBA decision; in addition, these programmes are also covered by patent filings that are unrelated to those involved in the current hearings.

“We are committed to building value in our telomerase technologies through development of our own product candidates as well as through licensing and partnerships,” continued Dr Earp. “Securing and enforcing our core intellectual property rights is key to all of these opportunities.”

Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases. The company is advancing anti-cancer therapies through multiple phase II clinical trials in different cancers by targeting the enzyme telomerase and with a compound designed to penetrate the blood-brain barrier.

Source: Pharmabiz

Monday, May 9, 2011

Rheumatoid Arthritis: Beat the Pain Naturally

Rheumatoid arthritis treatment varies, but there have been a flurry of success stories in recent days. According to the “New York Times” European golfer José María Olazábal is returning to the game. As the Times reports, “After missing the Masters last year because of a resurgence of the rheumatoid arthritis that already had threatened his livelihood a decade ago, he is back in the field for the major tournament that he won in 1994 and 1999.” Incredibly more news just broke announcing rheumatoid arthritis sufferer Jeffrey Gottfurcht plans on scaling Mount Everest. Actress Kathleen Turner, also an RA sufferer, is rehearsing for a play and working long 12 hour days in spite of her RA.

If you are suffering from RA these triumphant stories may seem unbelievable, but in conjunction with medical treatment perhaps homeopathy may help treat the pain associated with RA. According to the CDC, an estimated 50 million Americans are living with some form of arthritis. Homeopathic treatment seems to have clinical benefits for rheumatoid arthritis. An exploratory double-blind, randomized placebo-controlled clinical trial was conducted to assess the benefits of homeopathic intervention in patients with stable, active rheumatoid arthritis who had been under conventional therapy.

“The findings confirm previous work demonstrating that therapeutic benefits do arise from processes within the homeopathic consultation involving communication skills, empathy, hopefulness, enablement and narrative competence. The homeopathic consultation necessitates a very detailed understanding of the patient and is a unique and personalized approach.” Further studies are required to investigate the specific beneficial elements inherent in the homeopathic consultation, which could be employed by other clinicians to maximize patient benefit.

The take away, homeopathy alone is not a cure, but within the supportive environment that included active consultation resulted in improvement in disease outcome scales, pain assessment scores, patient global assessments and negative moods


Source: Diggs Science

Asthma Pills Work, Goodbye Inhalers!

A new study reveals that asthma pills work just as well as inhalers and might be easier to take.  Especially good news to hear since May is national Asthma Awareness Month.  Asthma is defined as a lung disease that inflames and narrows the airways, causing recurring periods of wheezing.

If you’re hesitant to pass up your inhaler just yet, here are some at-home remedies that could help your suffering.

Home Tricks to Curb Asthma Attacks

  1. Take vitamin D. Kids with asthma may breathe a sigh of relief — thanks to vitamin D. New research suggests that children with asthma who have higher vitamin D levels in their blood may be less prone to asthma exacerbation and have fewer asthma related hospitalizations than children with lower levels.
  2. Play a wind instrument. An Australian study suggests that playing the wind instrument the didgeridoo improves respiratory function in asthmatics over time. If your child suffers from asthma, there is a chance that the breath control it takes to play a wind instrument might just improve his symptoms. A similar study presented in the Journal of Asthma that incorporated a control group supports their results. The students that played wind instruments had a significant decrease in asthma symptoms and anxiety compared to the students who played non-wind instruments.
  3. Try the Mediterranean diet. Stronger adherence to a Mediterranean dietary pattern rich in fruits, vegetables and fish was associated with lower prevalence of wheezing in the past 12 months.  The Mediterranean diet is rich in fruits, vegetables, whole grains, fish, nuts and other foods high in healthy, monounsaturated fats, omega-3 fatty acids, fiber, and antioxidant vitamins A, C and E.
  4. Eat together as a family. One research study suggests family mealtime helped curb the frequency of asthma attacks.

Source: DIGGS Science

Making the Move to Exercise for Overweight and Obese People

How much exercise are overweight and obese people getting? More than many might think, according to research findings by nurses from Case Western Reserve University's Frances Payne Bolton School of Nursing.

They reported their findings in the Journal of the American Academy of Nurse Practitioners.

Deborah Walton Smith, who is now a senior lecturer at Gonzaga University, undertook the exercise study while a graduate student at Case Western Reserve. Also collaborating on the study were Joyce Fitzpatrick, the Elizabeth Ford Professor of Nursing, and Mary Quinn Griffin, assistant professor of nursing at Case Western Reserve.

Researchers surveyed the activities and intensions of 175 overweight and obese people who visited clinics run or owned by nurse practitioners in Spokane, Wash. Those individuals, who answered questions on several behavior tests, were 40 years old or older and had a Body Mass Index (BMI) of 25 or higher -- the range for overweight and obese.

The investigators found that 29 percent had been exercising for six months, 39 percent regularly exercised and 25 percent contemplated exercising.

Only 12 percent had no desire or thoughts of getting active.

The findings are important to combat obesity health issues.

According to the Center for Disease Control and Prevention, 34% of the population is obese, and the condition results in some 300,000 premature deaths annually due to diabetes, hypertension and coronary heart disease -- all related to overweight issues. Secondary to the obesity problem is sedentary lifestyles.

Little information is available about the exercise habits of overweight and obese individuals visiting nurse practitioners. The study provides information to help enhance practices by these health professionals.

The level of obesity was higher than expected; many patients had a BMI at or above 31. A BMI score between 25 and 29.9 is considered overweight and those at or above 30 are in the obesity range. Individuals were grouped in three classes of obesity, based on BMI scores from low (30-34.9), medium (35-39.9) and high (greater than 40).

Surprised by the level of exercise reported, Quinn Griffin said this study shows that just because someone is overweight does not mean they are not exercising or considering it.

Those with lower BMI scores in the obese range tended to exercise more. "This verified other research information that the higher their BMI, the less active people were," Quinn Griffin said, adding this is reflective of the overall population.

Quinn Griffin also explained that the more one exercised, the more benefits individuals saw in being active.

The research offers information for NPs who see overweight or obese patients, may help them make decision about exercising, and then follow up on those intentions at future visits.

Quinn Griffin said nurse practitioners, who see patients for routine health visits and checks ups, have an opportunity to help people move from contemplating exercising to starting.

She added that because a nurse practitioner knows the individual's health condition, the health professional can tailor an exercise routine to benefit particular needs.

"They can also encourage taking small steps like starting out walking," she said.

The study's participants were also asked if they had a dog at home. More than half did. A pet dog offers a beneficial reason for both the dog and person to take a walk.

Another small step can be to encourage individuals to purchase a pedometer. Only 28 percent of those surveyed reported owning one. Many do not realize how far they can walk in a short period of time, Quinn Griffin explained.

Source: ScienceDaily

Epigenetic Study Reveals New Insights Into Breast Cancer

The most comprehensive analysis yet of the epigenetic modifications present in breast cancer has revealed potentially important new ways to detect and treat the disease, Belgian researchers have reported.

Epigenetics is a term used to describe modifications to the DNA molecule that affect way its code is translated into proteins. These changes include methylation, a form of chemical modification.

Although researchers knew epigenetics was important in cancer, information about its exact contribution to breast carcinogenesis was scant, Dr Sarah Dedeurwaerder, from Université Libre de Bruxelles, in Brussels, explained at the IMPAKT Breast Cancer Conference.

"Our goal was to assess the epigenetic differences between normal tissue and primary tumor samples on a genome-wide scale, similarly to what has been done for gene expression patterns," Dr Dedeurwaerder said. "Here, we provide a glimpse to what DNA methylation profiling of primary breast tumors might bring to our understanding of their biology and diversity… that should contribute to better management of breast cancer patients."

The researchers performed a comprehensive DNA methylation profile on two independent sets of frozen breast tissue samples: a 'main set' of 123 samples, and a 'validation set' of 125 samples.

Their first finding was two major sub-types of breast cancer, defined according to whether the cancer expresses receptors for estrogen, are widely epigenetically controlled. "When we performed a clustering analysis of our samples based on their DNA methylation profiles, tumors segregated naturally into two distinct groups," Dr Dedeurwaerder said.

The first group was mainly composed of estrogen receptor-negative tumors, and the second one of estrogen receptor-positive tumors. "This indicates that ER-negative and ER-positive tumors have very different methylation profiles," she said.

"Furthermore, when we looked at more than 400 genes whose expression is positively or negatively correlated to the expression of the ER gene, we showed a reverse correlation between methylation and expression status of the majority of these genes. This suggests that epigenetics is probably involved in the regulation of expression of genes playing an important role in the establishment of the two major phenotypes of breast cancer determined by ER status."

The analysis also revealed new information about new sub-types of breast cancer. The researchers showed that DNA methylation profiles enabled breast tumors to be classified in more groups than those currently defined.

"This is really the most interesting part of these data," Dr Dedeurwaerder said. "Indeed, several patients displaying the same known sub-type of breast cancer can respond differently to a given drug. An epigenetic difference between the tumors of these patients might explain the difference observed in terms of treatment response. Therefore, DNA methylation profiling could help to refine the current breast cancer classification and thus might help to stratify patients within a particular sub-type both in terms of prognosis and prediction to treatment response."

"I think we can harness epigenetic information to improve cancer care in several ways," Dr Dedeurwaerder said. "Firstly, several lines of evidence suggest that epigenetic dysregulation occurs early during carcinogenesis and can be detected in bodily fluids. Therefore, DNA methylation markers could help to provide an earlier detection of the disease."

"Secondly, it has already been shown that DNA methylation markers might help to better stratify patients in terms of prognosis. Thirdly, such markers could also help to predict response to a given drug."

"Lastly, an epigenetic therapy of cancer, alone or in combination with conventional therapies, is conceivable," Dr Dedeurwaerder said. "Indeed, several drugs have been developed and several clinical trials have already shown promising results, in particular for leukemia."

"In this study, we have generated the largest and most comprehensive DNA methylation dataset for human breast tumor tissues," the researchers conclude. "By laying the ground for better understanding of breast cancer heterogeneity and improved tumor taxonomy, the precise epigenetic portraits drawn in our work should contribute to better management of breast cancer patients."

Commenting the study, which he was not involved in, Prof Fortunato Ciardiello, from Seconda Università di Napoli, Naples, Italy, noted that gene expression profiles by microRNA analysis have allowed to identify sub-groups of human breast cancers with different biological behaviors and eventually different prognosis.

"Now, for the first time, whole genome epigenetic analysis reveals, in a large number of human breast cancers, a series of sub-types which could help better define more homogeneous groups, which could be useful to select appropriate and more personalized therapeutic approaches."

Source: ScienceDaily

HIV Drug Could Prevent Cervical Cancer, Researchers Discover

A widely used HIV drug could be used to prevent cervical cancer caused by infection with the human papilloma virus (HPV), say scientists.

University of Manchester researchers, working with colleagues in Canada, have discovered how the antiviral drug lopinavir attacks HPV by switching on a natural viral defence system in infected cells.

The study, published in the journal Antiviral Therapy, builds on the team's previous work in 2006 that first identified lopinavir as a potential therapeutic for HPV-related cervical cancer following laboratory tests on cell cultures.

"Since publishing our earlier work, we have now found that lopinavir selectively kills HPV-infected, non-cancerous cells, while leaving healthy cells relatively unaffected," said Dr Ian Hampson, from Manchester's School of Cancer and Enabling Sciences.

"This is a very significant finding as these cells are not cancer cells but are the closest thing to being like the cells found in a pre-cancerous HPV infection of the cervix. In addition we were also able to show that lopinavir kills these HPV-infected cells by re-activating a well-known antiviral system that is suppressed by HPV."

In many developing countries, HPV-related cervical cancer is still one of the most common women's cancers accounting for approximately 290,000 deaths per year worldwide. The same virus also causes a significant proportion of cancers of the mouth and throat in both men and women and this disease is showing an alarming increase in developed countries, such as the UK, where it is now more than twice as common as cervical cancer.

Although in the developed world vaccination programmes against HPV are well underway, these are not effective in women already infected with HPV. Furthermore, the current vaccines do not protect against all types of HPV and they are expensive, which will limit their use in countries with limited resources. A cheap and preferably self-administered treatment that could eliminate early-stage HPV infections before these have developed into cancers would therefore have distinct health advantages.

Dr Hampson said: "Our results suggest that for this drug to work against HPV it would be necessary to treat virus-infected cells of the cervix with roughly 10-15 times the concentration that is normally found in HIV-infected patients taking lopinavir as tablets. This implies that, for this treatment to work, it would need to be locally applied as a cream or pessary."

Co-author on the paper, Dr Lynne Hampson, added: "These results are very exciting since they show that the drug not only preferentially kills HPV-infected non-cancerous cells by re-activating known antiviral defence systems, it is also much less toxic to normal non-HPV infected cells.

"Lopinavir is obviously safe for people to take as tablets or liquid but our latest findings provide very strong evidence to support a clinical trial using topical application of this drug to treat HPV infections of the cervix."

The research in Manchester was carried out by the Hampsons' PhD student, Gavin Batman, who was funded by the Humane Research Trust charity, with additional funding supplied by the Caring Cancer Trust and the Cancer Prevention Research Trust.

Source: ScienceDaily

India, Sri Lanka plan to work out mechanism to check export of substandard drugs by Indian pharma cos

Repeatedly faced with instances of supply of low-standard medicines and delay in supply of key medicines by Indian pharmaceutical firms, Sri Lanka is planning to take up the issue at the highest-level  through a meeting between the health ministers of both the countries.

Sri Lankan Health Minister Maithripala Sirisena is likely to visit Delhi this month to meet Union Home Minister Ghulam Nabi Azad on this issue, sources said. Both ministers are expected to discuss the recent controversies and sort out the problem by setting up some mechanism to prevent supply of substandard drugs and operation of spurious companies.

Sources also informed that Sri Lanka would not initiate any action or blacklist the Indian drug companies as now. But, Sri Lankan authorities will be handing over the details of the Indian companies under allegation to India during the visit. Based on the information, India will have to  take further action against such companies.

Recently, Sri Lanka had ordered the suspension of tenders awarded to 10 Indian drug companies for supplying sub-standard drugs, not adhering to tender procedures, and delaying deliveries. Indian High Commissioner had taken up the matter with the Lankan Minister. India had also assured action against the companies for allegedly violating the procedures.

India also proposed delegation from the Pharmaceuticals Export Promotion Council of India (Pharmexcil) visit Sri Lanka to meet the local Health authorities regarding the procedure adopted by the Sri Lankan government for sourcing pharmaceuticals from India.

As per the latest reports, Sri Lanka has made it clear that it would not blacklist the Indian drug suppliers and instead, the errant companies will have to forego the cash bond furnished in terms of the supply contract. The firms will accordingly be asked to forfeit the cash bonds between 5 to 10 per cent of the contract value, reports said. Around 100 Indian drug suppliers are in the Colombo Health ministry's suppliers’ roll.

Source: Pharmabiz

 

Abbott receives US FDA nod to expand use of RX Acculink Carotid Stent System to patients at standard surgical risk

Abbott announced that the US Food and Drug Administration (FDA) approved the RX Acculink Carotid Stent System for the treatment of patients with carotid artery disease who are at standard risk of adverse events from carotid endarterectomy (surgery). RX Acculink was previously indicated for patients at high risk of adverse events from surgery. This expanded indication is supported by the results of the CREST (Carotid Revascularization Endarterectomy vs. Stenting Trial) study. RX Acculink, used with the RX Acculink Embolic Protection System, represents an important option for standard-risk patients for the treatment of carotid artery disease.

"The CREST data demonstrated that carotid artery stenting is a safe, effective and minimally invasive treatment for standard-risk patients with carotid artery disease," said L N Hopkins, M.D., Professor and chairman, department of neurosurgery, and Professor of Radiology, State University of New York at Buffalo. "With this broader indication, the RX Acculink Carotid Stent System will become an important option for physicians as they determine the most appropriate treatment approach for their patients."

As part of its submission for an expanded indication, Abbott submitted the results of the CREST study, which is the largest prospective study conducted to date comparing carotid artery stenting to surgery. CREST was sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), and was partially funded by Abbott. The trial demonstrated that carotid artery stenting and carotid surgery had similar safety and long-term outcomes for standard-risk patients with symptomatic and asymptomatic carotid artery disease.

"FDA approval of the RX Acculink Carotid Stent System for patients at standard risk of surgery has the potential to significantly impact the treatment of patients with carotid artery disease," said Charles A. Simonton, M.D., FACC, FSCAI, divisional vice president, Medical Affairs, and chief medical officer, Abbott Vascular. "More than 60 per cent of US patients with carotid artery disease are at standard surgical risk, many of whom require a procedure to open the narrowed arteries that lead to the brain. This expanded indication for Abbott's RX Acculink provides these patients with an additional treatment option."

Abbott intends to seek expanded Medicare coverage for carotid stenting based on the CREST trial results. In addition, the company plans to initiate a post-approval study of the RX Acculink Carotid Stent System in patients at standard surgical risk later this year. The study is planned to assess clinical outcomes at 30 days and annually for three years.

The RX Acculink Carotid Stent System, used in conjunction with the RX Accunet Embolic Protection System, is indicated for the treatment of patients at high risk and standard risk of adverse events from carotid endarterectomy who require carotid revascularization (a procedure to restore blood flow) and meet certain criteria.

Abbott Vascular is a global leader in cardiac and vascular care with market-leading products and an industry-leading pipeline. Abbott Vascular offers a comprehensive cardiac and vascular devices portfolio, including products for coronary artery disease, vessel closure, endovascular disease, and structural heart disease.

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries.

Source: Pharmabiz

Cephalon presents positive phase IV results with Nuvigil in largest shift work disorder trial

Cephalon, Inc. announced that it had presented positive results from a phase IV trial of nearly 400 people with excessive sleepiness associated with shift work disorder at the Society of General Internal Medicine's 34th Annual Meeting in Phoenix, Arizona. In the trial, Nuvigil (armodafinil) tablets [C-IV] improved shift-workers' overall clinical condition late in their shifts (i.e., 4:00 a.m. to 8:00 a.m.), including the commute home, compared to placebo. The key secondary endpoint of the study was to assess global function, as measured by the Global Assessment of Functioning (GAF), and patients taking Nuvigil experienced a greater improvement in GAF score compared to those patients taking placebo. Shift work disorder occurs when the body's internal sleep-wake clock is out of sync with the individual's work schedule - their bodies tell them to go to sleep when their work schedule needs them to stay awake. The primary symptoms of shift work disorder are excessive sleepiness and insomnia.

This six-week, double-blind, placebo-controlled study of 383 patients with excessive sleepiness associated with shift work disorder was conducted at 45 sites across the United States. Participants in the study spanned a wide range of occupations associated with shifts or non-traditional work hours, including transportation and material moving, healthcare support, protective services, management roles and office and administrative support. For the primary endpoint, physicians used the Clinical Global Impression of Change (CGI-C) scale to evaluate the change from baseline (beginning of the study) in overall clinical condition late in the shift - from 4:00 a.m. to 8:00 a.m. The observation period also included the participant's commute home from work. Using the CGI-C rating, at the final visit, 77 percent of patients taking the recommended Nuvigil dose of 150 mg (n=177) improved, compared to 57 percent of patients taking placebo (n=182) - a significantly greater improvement (p<0.0001). These clinical data build upon the findings from the pivotal phase III study of Nuvigil in patients with excessive sleepiness associated with shift work disorder.

The key secondary endpoint in this trial was the Global Assessment of Functioning or GAF, a well-recognized assessment of patient functioning found in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, which evaluates an individual's social, occupational, and psychological functioning on a scale of 1 to 100. Scores above 70 on the Global Assessment of Functioning may be considered within the normal range of functioning. This study was the first to use the GAF to provide an assessment of functioning in patients with excessive sleepiness associated with shift work disorder. In this trial, physicians used the GAF to measure a patient's overall level of functioning at baseline and at the final visit. At baseline, patients in both the placebo and Nuvigil groups were rated an average score of 63, which is indicative of functional impairment associated with shift work disorder. Patients treated with Nuvigil experienced a 9.5 point improvement over baseline in the Global Assessment of Functioning, to mean scores of 72.6 at the final visit, compared to a 5.2 point improvement to means scores of 67.9 in those taking placebo at final visit (p< 0.0001).

"This study is important because up to 25 percent of people who work nights, early mornings, or other nontraditional shifts may be affected by shift work disorder. This condition affects their ability to function at work and at home, but they still need to do their jobs. The results of this study show an improvement in condition as well as a reduction in the impairment of patients treated with Nuvigil for excessive sleepiness associated with shift work disorder when compared to placebo," said Milton K. Erman, M.D., study lead investigator. Dr. Erman is a Clinical Professor of Psychiatry at the University of California San Diego and President, Pacific Sleep Medicine Services, San Diego, CA. "This study reinforces the need for healthcare professionals to learn more about this disorder and about how treatment options like Nuvigil may be of help in managing excessive sleepiness due to shift work disorder."

The most frequently reported adverse events in this study are similar to those described in the Nuvigil prescribing information, and include headache, nausea, and insomnia. There were no serious adverse events observed in patients taking Nuvigil in this study. This is the first presentation of these data at a medical meeting and additional results will be submitted for future publications and presentations.

According to the US Department of Labor, over 15 million Americans work odd hours or non-traditional shifts, and are "at risk" for shift work disorder. Approximately 10 - 25 percent of shift workers are estimated to have shift work disorder. People with shift work disorder often struggle to stay awake during their waking hours (excessive sleepiness), or have trouble sleeping during their sleeping hours (insomnia).

Nuvigil is indicated to improve wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD), treated obstructive sleep apnea (OSA), or narcolepsy. In patients with OSA, Nuvigil is used along with other medical treatments for this condition. The Nuvigil (armodafinil) label includes a bolded warning for serious or life-threatening rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment, that has been reported in adults in association with the use of modafinil and armodafinil and in children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in Nuvigil). Nuvigil is not approved for use in pediatric patients for any indication.

The most common adverse events in controlled clinical trials (five percent or greater) were headache, nausea, dizziness, and insomnia.

Cephalon is a global biopharmaceutical company dedicated to discovering, developing and bringing to market medications to improve the quality of life of individuals around the world. Since its inception in 1987, Cephalon has brought first-in-class and best-in-class medicines to patients in several therapeutic areas.

Source: Pharmabiz

Metabolon's metabolomics methods for drug discovery receives US patent

Metabolon, Inc., the leader in metabolomics, biomarker discovery and biochemical analysis, announced that it was awarded US Patent 7,910,301 “Methods for Drug Discovery, Disease Treatment and Diagnosis Using Metabolomics” by the United States Patent and Trademark Office on March 22, 2011. This is the ninth patent to issue from the fundamental Daouk-Kristal “metabolomics methods” patent family.

The ‘301 patent is directed to identifying small molecules that are affected by a drug or a toxin using metabolomics. It provides a method to evaluate chemical agents for drug effects and toxicity, thereby facilitating pre-clinical and clinical drug development activities. The patent extends Metabolon’s IP related to the use of metabolomics beyond disease biomarker discovery into uses of metabolomics for drug discovery and development.

Metabolon is the exclusive license holder of the Daouk-Kristal patent family which is comprised of early, pioneering patents and patent applications which provide fundamental IP in the field of metabolomics. Metabolon’s previously issued patents include the use of metabolomics for determining biomarkers for all diseases, including cancer, metabolic disorders, and neurological disorders such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, depression and schizophrenia. Metabolon also owns patents relating to disease biomarkers and for software designed for analyzing metabolomics data.

Metabolon, Inc. has advanced the field of metabolomics by pioneering and patenting the industry’s leading biochemical biomarker discovery and profiling platform. It has developed the technology to quickly identify and measure all of the biochemicals in a biological sample through its proprietary global processing method.

Source: Pharmabiz

 

 

Boston Scientific begins launch and first implants of next-generation devices to treat heart failure & sudden cardiac death

Boston Scientific Corporation announced the launch and first implants of its Energen and Punctua cardiac resynchronization therapy defibrillators (CRT-Ds) and implantable cardioverter defibrillators (ICDs) in Europe and other international markets. They are the world's smallest and thinnest high-energy devices to treat heart failure and sudden cardiac death and offer excellent longevity.

"These devices build on the technological advancements of Cognis and Teligen by providing options to customize therapy for individual patients," said Professor Joachim Winter, M.D., who performed one of the first implants of the Energen ICD with Dong-In Shin, M.D., at the University Hospital Dusseldorf in Germany.  "The small profile, coupled with the 4-SITE connector system, allowed for an easy implant with a less pronounced physical appearance for the patient."

"Physicians and patients will truly appreciate the longevity of these devices since it may reduce the need for additional implant surgeries," said Peter Lecher, M.D., who performed one of the first implants of the Energen CRT-D with Gunther Prenner, M.D., at the Medical University in Graz, Austria.  "Additionally, the new therapy options, combined with the Latitude Patient Management system, increase the variety of diagnostic parameters to help treat heart failure patients."

Most of the new Energen and Punctua devices offer the 4-SITE DF4 connector system option, designed to simplify the implant procedure and comply with international connector standards.  Additionally, nearly all models are compatible with Boston Scientific's Latitiude Patient Management system, which enables physicians to remotely monitor implantable cardiac device patients between on-site office visits.

"The Energen and Punctua devices are designed to improve the ability of physicians to deliver effective patient care," said Hank Kucheman, executive vice president and group president, cardiology, Rhythm and Vascular for Boston Scientific.  "This new portfolio of products, built on our tradition of innovation, continues our advantages in size, shape and longevity and provides multiple therapy options to match specific patient needs."

The company received CE Mark approval for its Energen and Punctua CRT-Ds and ICDs in October 2010.  In the US, they are investigational devices, limited by applicable law to investigational use and not available for sale.  The company expects Food and Drug Administration approval for the devices in late 2011 or early 2012.

Boston Scientific is a worldwide developer, manufacturer and marketer of medical devices whose products are used in a broad range of interventional medical specialties.

  Source: Pharmabiz


Saturday, May 7, 2011

Regenerative medicine: a new era

 The human quest for knowledge has led to many discoveries, which from time to time has changed our outlook towards our environment and life itself. Stem cells are one such discovery.

Not a single month passes on without a new stem cell research paper being published. Stem cells offer exciting medical promise for repairing or replacing organs that are diseased, damaged or worn out. This promise of repair and regeneration was taken a step further with the advent of Adipose (Fat) Derived Stem Cells (ADSC) which are derived from our own excess body fat.

Much like recycling waste, our excess fat can be processed to give us a better quality of life. Currently used for breast augmentation and reconstruction as well as plastic surgery, ADSC are being researched for most debilitating diseases like Myocardial Infarction (MI), diabetes mellitus, and neurodegenerative diseases also.

Growing interest

There has been growing interest in the promise of ADSC. About eight years ago, 300 scientists from around the world came together to form the International Federation of Adipose Therapeutics and Science Society, to share their knowledge and experience. Subsequently, many researchers in India are also studying the effect of ADSC in various diseases. Researchers feel that a growing number of liposuction procedures prompted the study of ADSC. Expressing his views about this trend Dr Samuel JK Abraham, Director, Nichi-In Centre for Regenerative Medicine (NCRM), Chennai says, "I guess its because of the growing number of liposuction procedures mainly for aesthetic reasons during which significant quantity of adipose tissue is removed, which instead of being discarded, could become an useful source of stem cells, for storage and future applications."

Celution system
A surgeon harvests a small amount of adipose tissue from the patient, or fat as it is more commonly know.  The surgeon then places the fat into the Celution system.  The system then processes the fat and in 90 minutes provides the surgeon with a five cc heterogeneous population of the patient's own regenerative cells to be used to treat an ischemic disease.  This five cc syringe of autologous regenerative cells can be mixed back with the patients fat cells to create a cell-enriched fat graft, or used independently depending on the presenting case. Celution system is a combination of capital equipment and a per-patient consumable set.  The system was designed for the operating room or cardiac cath lab and designed to vertically integrate into the operating room workflow.  The system is the culmination of a decade of research and development that is now being used through Europe, Japan, the US and India.

Added advantage

Another reason for growing interest in ADSC is the ease of the procedure and advantages over Bone Marrow Derived Stem Cells (BMDSC). According to a review published by Helder, et al ADSC has several advantages over BMDSC, such as easy accessibility; minimal morbidity upon harvest. Additionally, clinically relevant stem cell numbers can be extracted from adipose tissue isolates, potentially eliminating the need for in vitro expansion. Also ADSC have higher stem cell proliferation rates than bone marrow mesenchymal stem cells. The study also states that ADSC show potential for multiple differentiation as they differentiate in vitro and in vivo towards adipogenic, osteogenic, chondrogenic, myogenic, ligamentous, and probably, neurogenic, endothelial, hematopoietic and cardiomyogenic phenotypes.

"Clinically, ADSCs have the advantage over their bone marrow-derived counterparts, because of their abundance in numbers - eliminating the need for culturing over days to obtain a therapeutically viable number - and the ease of the harvest procedure itself - being less painful than the harvest of bone marrow. This, in theory, means that an autologous transplant of ADSC will not only work in much the same way as the successes shown using marrow-derived mesenchymal stem cell transplant, but also be of minimal risk to the patient," explains Dr Vijay Sharma, CEO, Kasiak Research Pvt Ltd, Mumbai.

Adding to this Dr Ramananda S Nadig, CEO, Khoday Stemcell Research & Medical Centre, Bangalore opines,"There is an obvious benefit of ADSC in cardiac disease going by the fact that it is easy to harvest and culture adipose tissue stem cells from the patient himself without subjecting him to invasive procedures of obtaining the stem cells from the bone marrow. This would be even more useful given the fact that following a MI one has to wait for sometime before performing a bone marrow aspiration."

However, with great discoveries comes great debate. Some researchers think it is too early to talk about the ADSC therapy, and want to wait for long-term study results. "Too early to say which therapy is better. Long term studies are essential to prove their efficacy against the bone marrow stem cells which are in clinical practice for bone marrow transplantation as well as primary organ failures for long," says Dr Abraham.

However other surgeons feel that BMDSC may have more merit over ADSC. "The bone marrow has relatively less number of mesenchymal stem cells but it has a different cocktail of stem cells, namely endothelial progenitor and haematopoietic stem cells. It also has abundant quantity of growth factors which are necessary for cell proliferation and differentiation. This cocktail of different cells helps in multiplication of these cells. It has been seen that more pure the cell types, poor are the results," opines Dr Himanshu Bansal, Medical Director, Anupam Hospital, Uttrakhand. Having worked on comprehensive treatment with autologous tissue like BMDSC, sural nerve graft, nasal olfactory tissue and omental transposition for treatment of spinal cord injury, Dr Bansal also says, "All indication served by mesenchymal stem cells of bone marrow can be served by ADSClike spinal cord injury, neurodegenerative disorders, cardiomyopathies, avascular necrosis of bone. Also ADSC are easy to isolate via less invasive process."

Process simplified

The process as described by various researchers is fairly simple. Doctors perform liposuction to remove a portion of fat about the size of a medium potato from, for example, the abdomen. They then extract the stem cells, and then inject them into diseased tissue. There's no chance of rejection since the cells come from the patient. The extract from liposuction may contain either a mixture of cells or can be pure stem cell, as required by the procedure. All this is achieved in less time and with minimum discomfort to the patient.

Utility galore

The safest procedure to use ADSC and adipose derived regenerative cells is cosmetic surgery for facial reconstruction and facial defect repair. The process has been approved in Europe and Japan and is now being used in India. This is followed closely by breast augmentation and reconstruction, wound healing as well as radiation lesions and Crohn's disease. One of the first surgeons to use this therapy, Dr Anup Dhir, Senior Consultant, Apollo Hospital, Cosmetic Plastic Surgeon & Andrologist and Secretary Indian Association of Aesthetic Plastic Surgeons says, "Fat grafting with adult stem cells and regenerative stem cells can rejuvenate the skin. Usually fat grafting is done in two to three sittings; however with this procedure once you add these cells the number of fat grafting required is less. The ADSC helps increase fat survival and improves result." He recently used this process on a 24-year-old patient who had windscreen injury to the right side of her face at the age of three. Since then, she underwent a number of surgeries, but her disfigurement and scars were not healed satisfactorily. However, after the procedure, Dr Dhir says, "A lot of improvement is seen in this patient in last four months, scars have become lighter so much so that its just noticeable. ADSC stimulates angiogenesis (formation of new blood vessels) and thus fills cavities and improves scars. There is nothing artificial, nothing synthetic so no side effects. Plus this therapeutic application is a well established procedure."

"I was a part of adipose tissue derived stem cell trial in spinal cord injury and critical limb ischemia. We could not have a large number of subjects because of cost considerations, but the results were encouraging in spinal cord injury.However in critical limb ischemia results were poor as compared to good results of other studies with bone marrow derived stem cells," laments Dr Bansal.

"A 32-year-old patient with complete spinal cord injury showed phenomenal improvement after stem cells injection from adipose derived source. His bladder and bowel control and walking index improved significantly over a six month period. Three out of seven patients with spinal cord injury showed improvement. We will compare this result with a present ongoing trial with bone marrow cells," Dr Bansal further adds.

Celution has been reviewed and approved for use in Europe by CE Mark

The CE Mark enables Cytori to market Celution under the follow:  
The Celution 800/CRS System is indicated for:       

Plastic & Reconstructive Procedures to replace, repair, reconstruct, or augment:         

Surgical soft tissue defects (defect up to 150 mL in size and augment up to 260 mL of volume),        
Such as those seen in the breast due to mastectomies and lumpectomies          
Liposuction defects, such as those seen in the abdomen, back, thighs and buttocks          
Congenital asymmetry of soft tissues, such as those seen in the breast, buttocks and face         
Soft tissue wasting disorders, such as those affecting the hands and face       

The Celution 800/GP System is indicated for:

General surgery procedures to facilitate healing in: rectal and vaginal fistulae in Crohn's disease

Apart from these Mumbai based Kasiak Research Pvt Ltd, is using ADSC for idiopathic pulmonary fibrosis. "Kasiak has a novel technique for the isolation of ADSCs and the pilot studies so far have yielded encouraging results. The turn around in patients with terminal conditions such as IPF would be the highlight, but would also like to share the potential of this therapy in diabetic foot ulcers," informs Dr Sharma.

Apart from this there are a number of trials investigating applications in ischemic heart disease around the world. Six-month results from a 14-patient heart attack trial in the Netherlands and Spain showed not only a reduction in the size of the heart injury, but also improvements in the amount of blood supplied to the heart muscle and the amount of blood the heart can pump.Data from a second trial, a 27-patient chronic heart disease study in Spain, showed a reduction in the amount of damage in the left ventricle. It also showed that patients receiving stem cells had better oxygen consumption and improved ability to perform physical activity.

Unique preposition

Recently Apollo Hospital, Hyderabad announced that they would be using a unique equipment to bring stem cell therapy from bench-to-bed-side. The Celution system, patented by the US based Cytori Therapeutics, is the only medical device approved in Europe that offers hospitals and clinics the ability to extract stem and regenerative cells from fat (adipose) tissue in a sterile, cost-effective manner without time consuming manual processing. Dr Sudhakar Prasad ,Senior Consultant, Plastic & Cosmetic Surgeon, Apollo Hospitals in a press release said, "Apollo physicians have already performed several celution system based cell-enriched fat grafting cosmetic procedures such as breast augmentation and facial rejuvenation in Hyderabad and Delhi as part of the initial evaluation of the technology." He further added that this will bring in major advantages to patients particularly in areas of breast augmentation, face lifts and wound healing.

According to Cytori, Celution System is a point-of-care device that standardises and automates the extraction of naturally occurring stem and regenerative cells from the patient's fat tissue, the richest source of stem and regenerative cells in the body. Cytori's celution system is CE marked in the European Union for use in breast reconstruction, augmentation and other cosmetic and reconstructive procedures, said Apollo Hospitals. "A key advantage to ADSCs and Celution cell therapy technology is cell numbers and point-of-care, real-time access," says David Oxley, Vice President, Emerging Market Sales, Cytori Therapeautics, US

In addition to the above therapy, hospitals around the world are using Celution under physician initiated clinical trials to address such diseases as urinary incontinence, Parry-Romberg Syndrome, liver and kidney ischemia and HIV facial wasting.

Talking about the equipment Oxley further explains, "Celution system enables the surgeon in the operating room to harvest, process, and deliver his or her patient's own stem and regenerative cells to treat a wide variety of ischemic diseases. Apart from being the largest known source of stem and regenerative cells in the human body, fat is also a much easier source of tissue to harvest from patients in the operating room than bone marrow. Thus, why Cytori has designed its technological innovation around fat and the needs of an operating room - easy source of tissue to extract, largest known sources of stem and regenerative cells to draw from, and efficient for surgeons who demand real-time use across a wide variety of ischemic diseases."

"If the surgeon wants clinical grade regenerative cells to treat his or her patient without disruption of patient flow, operating room delay, or risk of tissue rejection, then Celution is the platform of choice," he further adds.

Adipose (fat) tissue-derived regenerative cells (ADRCs) obtained using the Celution System demonstrated a statistically significant improvement in cardiac functional capacity (MVO2) at 18 months in PRECISE trial for chronic myocardial ischemia. New data from this trial were presented at the American Heart Association Scientific Sessions 2010 in Chicago by Co-Principal Investigator Emerson C. Perin, MD, PhD, Director, Clinical Research for Cardiovascular Medicine, and Medical Director, Stem Cell Center, Texas Heart Institute.

The trial demonstrated the following outcomes in no-option chronic ischemic heart disease patients:

The statistically significant improvement in MVO2 (maximum oxygen consumption) in the cell treated group compared to the control group, first demonstrated at six months, is sustained at 18 months;

The statistically significant improvement in patients' ability to perform physical activity, as measured by metabolic equivalents (METS), in the cell treated group compared to the control group is sustained from 6 to 18 months; and

The procedure, which includes withdrawing fat tissue, separating out the regenerative cells using Cytori's Celution® System, and re-injecting the cells into the patient's heart, has previously been found to be safe and feasible, with no safety concerns emerging during the 18-month observation period.

ADRC treated patients had a lower cardiac mortality rate compared to the control. At an average follow up of 28 months, two of six placebo patients died of cardiac causes whereas one of 21 died in the cell treated group from cardiac causes. There were two patient deaths from non-cardiac causes in the cell treated group.

Based on this new information, Cytori will directly seek EU regulatory approval of this treatment for no-option chronic ischemia patients.

Apolitical cells

Researchers are of the opinion that ADSC are easy to use as there is no ethical issues involved as compared to embryonic stem cells. As ADSC come from the patients themselves and not from embryos that are destroyed in the process of extracting their stem cells, their use bypasses the ethical dilemmas that divides many researchers. "Against embryonic stem cells, its needless to say that adipose tissue derived cells have no ethical issue of destruction of a potential life for harvesting stem cells," explains Dr Abraham

Cost consideration

The procedure is expensive yet not marginally expensive compared to the existing procedures. New technology does incur cost. "The cost of any Stem cell therapy is almost the same as any conventional surgical procedure. It would perhaps cost as much as Rs 50,000-75000 for one course of Stem cell therapy and the number of courses and duration would obviously depend on patient improvement. The cost of therapy will depend on procedures involved in procuring the stem cells, harvesting, culturing and characterisation including quality control of all procedures. With increase in numbers and scale of operations the cos will come down over time," explains Dr Nadig.

Adding to this Dr Sharma says, "The cost would be determined once the trials have been successfully completed, but a good estimate would be Rs 1.5 lakh."

Impact

As can be seen, this therapy would positively impact the outcome of many diseases. Maybe in the years to come people will queue up for fat donation drives much like they queue up for blood donation now-a-days. The basis of this therapy is an autologus cell, which may be a stepping stone now yet in future it would encompass a broad array of technologies. Some researchers have compared this to the computer age before software and applications. People knew the computer was a powerful tool but did not have methods to harness its potential. However, today pretty much everything runs on computer software and its progenies.

Similarly, ADSC have the potential to impact our lives, if new tools and technologies for therapy are developed using this platform. Summing up the impact Dr Dhir says, "If it lives up to its initial expectation it will give rise to another dimension in medicine. Its application will be far more impactful in heart, knee and spinal indications."

Caution amid optimism

While many researchers are hopeful of ADSC therapy, some experts urge caution, saying it's too early to know whether these cells will be as good as other types of stem cells.

Primary concerns are related to the scientific pitfalls of stem cells giving rise to cancer, which is being studied by researchers. Another theoretical concern is that ADSC may cause fat to develop in grafted tissue. Studies to dismiss or support these theories have to be elucidated.Dr Bansal says, "ADSC therapy should be carried as clinical trial in few patients (maximum 20) in which sound preclinical data exists. Once the results are encouraging it should be published and a placebo-controlled, multicentric clinical trial on more number of patients should be done before taking it up as therapy."

Source: ExpressPharma

Protein Snapshots Reveal Clues to Breast Cancer Outcomes

 Measuring the transfer of tiny amounts of energy from one protein to another on breast cancer cells has given scientists a detailed view of molecular interactions that could help predict how breast cancer patients will respond to particular therapies.

At the IMPAKT Breast Cancer Conference in Brussels, Dr Gargi Patel from the Richard Dimbleby Department, King's College London, described cutting-edge research in which she and colleagues captured detailed information about protein interactions on cancer cells, and correlated that with established genetic markers for cancer spread.

Dr Patel's group used a microscope technique known as Foerster resonance energy transfer (FRET) imaging, which allows them to measure the interactions between two proteins.

In this technique, each of the proteins is labeled with a fluorescent tag --one might be labeled green and the other red, for example. A laser is used to excite one of these labels, which becomes excited and then decays back to its rest state in a specific lifetime, which the researchers define as its fluorescent lifetime.

When this label comes within a nanometer of the second label, exciting by the laser causes some of its energy to be donated to the other label, and the fluorescent lifetime of the first label becomes shorter. "In the context of our work, this process only occurs when two proteins are close enough to be interacting, and hence we can quantitate protein-protein interactions," Dr Patel explains.

In earlier work, Dr Patel's group used this technique on breast cancer cells in the lab to describe in detail the interaction between the cell-surface molecules Her2 and Her3 that is known to determine whether a cancer will respond to the drug lapatinib.

"We aim to establish a 'signature' representing functional molecular biology, by examining protein-protein interactions, and to correlate this signature with established prognostic gene signatures and clinical and radiological data to predict patient outcome in terms of likelihood of recurrence and response to treatment such as lapatinib," Dr Patel explains. "The results we present at IMPAKT are the start of this work."

"The work I am doing captures images of the molecular state of Her2-Her3 receptors as a dimer, and shows us the results of lapatinib treatment. We have also identified a specific mutation in Her2, which reduces dimerization and the lapatinib effect. We can test tumor samples for this Her2 mutation, which would confer resistance to treatment."

This technology could have a significant clinical impact, the researchers say, by improving the accuracy of predictions about a cancer's risk of spread or response to treatment.

"Currently our methods of prognosis estimation depend on clinical data such as tumor size and lymph node status, or upon correlation with genetic signatures which may delineate tumors with higher metastatic potential. However the accuracy of any single method is far from 100%. We aim to add to the tools available by introducing a signature reflecting the functional state of cancer cells, by assessing protein-protein interactions. We could integrate this information with genetic and clinical data to more accurately predict outcome," Dr Patel said.

Commenting on the study, which he was not involved in, Dr Stephen Johnston, from Royal Marsden NHS Foundation Trust & Institute of Cancer Research, noted: "Lapatinib is a novel drug to target Her2 positive breast cancer, and works in a different way to the established monoclonal antibody trastuzumab."

"It is recognized that other growth factor receptors in breast cancer such as Her3 can modulate how Her2 positive tumors respond, often making them resistant to trastuzumab. In contrast, these researchers have developed as assay to measure Her2/Her3 heterodimers and the molecular pathways that they activate in human tumors, and suggest that in future this assay could be used to predict for response to lapatinib in the clinic."

Source: ScienceDaily

Advanced Instrument Analyzes Immune Cells in Far More Detail: Technology Promises More Effective Prescription Drug Therapies

 Researchers at the Stanford University School of Medicine have taken a machine already in use for the measurement of impurities in semiconductors and used it to analyze immune cells in far more detail than has been possible before. The new technology lets scientists take simultaneous measurements of dozens of features located on and in cells, whereas the existing technology typically begins to encounter technical limitations at about a half-dozen.

The investigators were able not only to simultaneously categorize more immune cell types than ever before seen at once but, at the same time, to peer inside those cells and learn how various internal processes differed from one cell type to the next.

"We can tell not only what kind of cell it is, but essentially what it's thinking, what it's been doing, and what it may soon do or become," said Garry Nolan, PhD, professor of microbiology and immunology and the senior author of the study detailing the advance, to be published May 6 in Science.

With this new approach, the scientists were further able to show the unexpected effects of a drug recently approved for treating certain leukemias -- dasatinib -- on biochemical activities taking place inside various types of cells, offering a possible explanation for some of dasatinib's side effects as well as suggesting potential new uses for the drug.

In the study, Nolan and his colleagues simultaneously monitored 34 different substances found inside and on the surface of different cell types produced in human bone marrow, the place where all immune and blood cells, as well as blood disorders such as leukemia, originate.

By measuring large numbers of cell features all at once with the new technology -- called mass cytometry -- the team could capture subtle transitions between cell states in, essentially, a high-resolution snapshot of the entire blood-forming system, he said. Scientists normally think of the blood and immune cells as differentiating in a series of discrete steps. However, the authors showed that the transitions from one cell state to another are marked by gradually shifting levels of cell-surface markers and varying amounts and activation states of several intercellular molecules.

Mass cytometry builds on an established technology known as fluorescence-activated cell sorting, or FACS, which is in widespread use throughout the world. FACS was developed in the laboratory of Leonard Herzenberg, PhD, professor emeritus of genetics, under whose direction Nolan did his PhD work in the 1980s.

Both FACS and mass cytometry employ antibodies to specifically tag particular surface features on cells.

With traditional FACS, antibodies are designed to tag diverse cell features. Then the antibodies are affixed to differently fluorescent dyes that color-code these antibodies according to which cell feature they target. After being bathed in these antibody-dye preparations, cells are passed single-file through a tube and stimulated by laser pulses, which cause the dye molecules to give off bursts of light. Different wavelengths of light emitted by the dyes correspond to the cellular features the dyes have tagged. FACS technology, though over 30 years old, is a mainstay of immune studies, as well as cancer and vaccine research.

But researchers are eager to squeeze ever more information out of each cell they examine. This requires examining ever more cell features at once, and there are only so many colors in the rainbow. The ability of FACS to distinguish between any more than a half-dozen dyes is constrained by those dyes' overlapping fluorescence patterns.

Three years ago, Nolan was approached by Scott Tanner, a physical chemist now at the University of Toronto.

"He buttonholed me at a meeting," said Nolan, laughing. "I was trying to get away from him, but after he'd been talking for a few minutes I realized this was something I'd better start paying attention to. He clearly had something that, if true, was revolutionary in its potential."

Tanner's team was adapting for biological purposes an existing instrument that is typically used for gauging precise levels of added rare-earth impurities in semiconductors and for geological purposes. The new instrument, called a mass cytometer, promised to more than double the number of molecular features that could be measured simultaneously in each cell. Nolan, realizing that such an instrument could be used to learn much more about the immune system and cancer stem cells, was eager to bring his group's expertise to bear on its development. The Stanford team has worked in close collaboration with the new instrument's developers ever since.

Instead of dyes, mass cytometry joins rare-earth metals to antibodies, which in turn detect cellular features and processes. "The rare earths are a series of 17 elements, mostly at the bottom of periodic table, that nobody wanted to learn about in chemistry class, myself included," said Sean Bendall, PhD, a postdoctoral researcher in Nolan's lab. However, these elements turn out to particularly useful for biological applications, said Bendall, who shared first authorship of the Science paper with Erin Simonds, a graduate student in Nolan's lab.

"They're not all that rare in nature, but they're normally never found in the body," Bendall said. "If I looked at a sample of your blood and found some europium or ytterbium or neodymium in it, I'd say you were in deep trouble." So rare-earth elements stand out in a crowd.

What's more, these elements can be subdivided into as many as 100 variants with distinct atomic weights. Mass cytometry can easily detect those differences. "We need relatively few rare-earth atoms per cell for our instrument to see them," said Bendall.

In mass cytometry, cells are paraded one by one through a tube and sprayed into a tiny chamber in which they are heated to about 13,000 degrees Fahrenheit and vaporized into successive clouds of atomic nuclei and loose electrons. Next, the contents of each cloud that was once a cell are essentially flung against a wall with equal force. The lightest atoms arrive first, then the next-lightest and so forth. A detector counts the atoms as they land, and from this the instrument can determine their mass. The mass tallies how many copies of each metal-tagged antibody were stuck to the cell and, therefore, how many copies of each molecular feature were present on, or in, the cell in the first place.

In the Science study, Nolan and his colleagues used the instrument to simultaneously monitor 13 separate molecular features on the surfaces of cells in samples taken from two healthy humans' bone marrow, and classified the cells into numerous distinct categories. The investigators simultaneously monitored activation states of 18 different intracellular protein targets. Protein activation levels give important clues about particular cellular decisions that have been or can be made, such as whether a cell is about to divide.

"As a prelude to looking at leukemic bone-marrow samples down the road, we wanted to first characterize the cells in normal bone marrow to see how their behaviors change as they mature," said Simonds.

The Nolan group perturbed cells by exposing them to various substances, including signaling molecules that sometimes circulate in our own blood, as well as foreign materials such as fragments of bacterial cell walls that are known to excite immune responses. "In essence," said Nolan, "we are interviewing or interrogating the cells, forcing them to reveal their inner thought processes." Some of these stimulatory tests were done in the presence of dasatinib, a drug used to treat chronic myelogenous leukemia and certain cases of acute lymphoblastic leukemia. Dasatinib is in clinical trials for several other indications, including some solid cancers.

When the Nolan group used a chemical, pervanadate, to "release the brakes" on a universal pro-cell-survival behavior, dasatinib blocked action in every cell type except one, the immune sentinels called dendritic cells. Simonds said this new finding demonstrates mass cytometry's capacity to ferret out tiny differences in cellular behavior that may help explain drugs' side effects as well as to indicate potential new uses for existing drugs.

The more measurements your tailor makes, the better the fit. It's the same with cell biology. "Our entire lab has already shifted from fluorescence-based measurements of cell features to this new MS-based method, because we get a much more complete picture," said Bendall.

Nolan has reported that he owns stock in the company Tanner created to develop and market the new system.

The study was sponsored by the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute and the Leukemia & Lymphoma Society. Other Stanford co-authors are senior research scientist Peter Krutzik, PhD; postdoctoral researcher Karen Sachs, PhD; data analyst Rachel Finck; research assistant Angelica Trejo; graduate student Robert Bruggner; associate professor of radiology Sylvia Plevritis, PhD; and former postdoctoral researcher Peng Qiu, PhD, now an associate professor at the University of Texas-MD Anderson Cancer Center.

Source: ScienceDaily

Parental Exposure to BPA During Pregnancy Associated With Decreased Birth Weight in Offspring

 Parental exposure to bisphenol A (BPA) during pregnancy is associated with decreased birth weight of offspring, compared with offspring from families without parental BPA exposure in the workplace, according to Kaiser Permanente researchers.

The observational study is published in the current online issueReproductive Toxicology.

Researchers explained that there was a greater magnitude of decrease in birth weight in children whose mothers were directly exposed to high BPA levels in the workplace during pregnancy, followed by those whose mothers were exposed to low levels of BPA in the workplace, then by those whose mothers had BPA exposure through father's high occupational BPA exposure, and finally, the least decrease in birth weight in the offspring whose mothers had BPA exposure through father's low occupational exposure.

Although the finding needs to be confirmed by additional studies, the study provides preliminary evidence that maternal exposure to BPA during pregnancy may have an adverse effect on fetal growth, said De-Kun Li, MD, PhD, the principal investigator of the study, senior author of the new publication, and a reproductive and perinatal epidemiologist at the Kaiser Permanente Division of Research in Oakland, Calif.

Exposure to BPA has been reported to reduce birth weight in animal studies at relatively high levels of exposure. Both animal and human studies have shown that BPA can pass through the placental barrier and that fetuses are likely to be exposed to similar (if not higher) levels of BPA as those of mothers, explained the researchers.

The study population was identified from a larger study of more than 1,000 male and female workers in factories in China. It compared workers in BPA-exposing facilities with a control group of workers in factories where no BPA was present. BPA-exposed (from the manufacturers of BPA and epoxy resin) and unexposed workers (from industries without BPA exposure), including their spouses and offspring, were recruited from 2003-2008.

Mothers in the mother-exposed group worked for at least three months during pregnancy. The researchers explained that it is possible that offspring in this group had relatively higher levels of in-utero BPA exposure than those in other groups. Spouses of exposed fathers, although not directly exposed to BPA in the workplace, were more likely to have a higher BPA exposure level than women in the unexposed group. Exposure in this group could occur through exposure to contaminated clothing, through workplace visits with spouses, and through residence proximity to factories, explained the researchers.

This study is the fourth in a series published by Dr. Li and his colleagues that examine the effect of BPA in humans. The first study, published in November 2009 in the Oxford Journals' Human Reproduction, found that exposure to high levels of BPA in the workplace increases the risk of reduced sexual function in men. The second study, published in May 2010 in the Journal of Andrology, found that increasing BPA levels in urine are associated with worsening male sexual function. The third study, published in Fertility and Sterility, showed that an increasing urine BPA level was significantly associated with decreased sperm concentration, decreased total sperm count, decreased sperm vitality and decreased sperm motility.

Funded by the U.S. National Institute of Occupational Safety and Health, this latest study adds to emerging human evidence questioning the safety of BPA, a chemical created in the production of polycarbonated plastics and epoxy resins found in baby bottles, plastic containers, the linings of cans used for food and beverages, and in dental sealants.

The researchers explained that BPA is believed by some to be a highly suspect human endocrine disrupter, likely affecting both male and female reproductive systems. These findings provide epidemiological evidence that has been lacking as the U.S. Food and Drug Administration and various other U.S. government panels have explored this controversial topic.

The present study was limited by the small sample size in the exposed group. Due to the retrospective nature of the study, estimated exposure levels in the past, rather than maternal urine BPA level, was used to classify the exposure dosage during the index pregnancy. Although researchers have demonstrated that the estimated BPA exposure was correlated with current urine BPA, it is still possible that the association between BPA exposure and birth weight was impacted due to inaccurate classification of BPA exposure categories.

Other authors on this study include: J.R. Ferber, MPH, and L.J. Herrinton of the Kaiser Permanente Division of Research; Z. Zhou, PhD, MD, and Y. He, PhD, of the Department of Occupational Health and Toxicology, School of Public Health and WHO Collaborating Center for Occupational Health, Fudan University, Shanghai, China; M. Miao, PhD, J. Wang, PhD, E. Gao, MD, MPH, PhD, and W. Yuan of Shanghai Institute of Planned Parenthood Research and National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices.

Source: ScienceDaily

Cancer Researchers Link Ovarian Hormone to Breast Stem Cells Growth

 Cancer researchers at Princess Margaret Hospital (PMH) have discovered that the ovarian hormone progesterone plays a pivotal role in altering breast stem cells, a finding that has important implications for breast cancer risk.

The findings, published online inNature, are significant because reproductive history is among the strongest risk factors for breast cancer, says principal investigator Rama Khokha, a molecular biologist at Ontario Cancer Institute and the Campbell Family Cancer Research Institute, PMH. Other major known risk factors are age, genetics and breast density.

"Our study shows how and when hormones affect breast stem cells during the natural reproductive cycle. There are well accepted links between ovarian hormones and breast cancer, and there is mounting evidence that stem cells are seeds for breast cancer. We now show a direct connection between hormones and breast stem cells. "

Lead author Purna Joshi adds: "Our research demonstrates that when progesterone peaks during the second half of the menstrual cycle, it starts a cross-talk between stem cells and neighbouring cells that propels normal breast stem cells to expand in number, and may trigger an environment where cancer can begin."

Until now, breast stem cells were thought to be generally inactive in the adult female breast, says Dr. Khokha, whose speciality is modelling human cancer in the laboratory. In this study, the research team replicated the human natural reproductive cycle in mice to determine the impact of hormones on breast stem cells.

How hormones change these stem cells opens a new pathway to understanding the cell growth that begins breast cancer, and, with further research, will open new ways of targeting stem cells.

"It is the first evidence, to our knowledge, for progesterone-driven dynamic shifts in the mammary stem cell pool. This activation provides an opportunity to start the process of cell transformation leading to breast cancer."

The research was also supported by the Canadian Cancer Society Research Institute and the Canadian Breast Cancer Foundation.

Source: ScienceDaily

Normal Stem Cells Made to Look and Act Like Cancer Stem Cells

 Researchers at the University of North Carolina at Chapel Hill School of Medicine, after isolating normal stem cells that form the developing placenta, have given them the same properties of stem cells associated with an aggressive type of breast cancer.

The scientific first opens the door for developing novel targeted therapies aimed at triple negative breast cancer. Known also as TNBC, this is a highly recurrent tumor that spreads aggressively beyond its original site in the breast and carries a poor prognosis for patients who have it.

The study will be published online on May 6 by the journal Cell Stem Cell.

"We changed only one amino acid in normal tissue stem cells, trophoblast stem cells. While they maintained their self-renewal, these mutant stem cells had properties very similar to what people predict in cancer stem cells: they were highly mobile and highly invasive," said Gary Johnson, PhD, professor and chair of pharmacology at UNC and senior study author. "No one has ever isolated a stem cell like that." Johnson is also a member of the UNC Lineberger Comprehensive Cancer Center.

In normal development, epithelial stem cells called trophoblasts are involved in the formation of placental tissue. To do so, they must undergo a conversion to tissue-like cells. These then travel to the site in the uterus where they revert to a noninvasive tissue cell. "But the mutant trophoblast stem cells made in our lab, which would normally invade the uterus and then stop, just keep going," Johnson said.

The study led by the first authors, research assistant professor Amy N. Abell, PhD and graduate student Nicole Vincent Jordan, both working in Johnson's lab, showed that similar to triple-negative breast cancer stem cells, normal tissue stem cells also go through the same program of molecular changes during organ development called epithelial mesenchymal transition, or EMT. This suggests that breast cancer cells utilize this tissue stem cell molecular program for tumor metastasis, or cancer spread.

The discovery was made using a unique mouse model of tissue stem cell EMT developed in the Johnson laboratory. The study identified two proteins that regulate the expression of specific genes in tissue stem cells during organ development that control normal EMT. Inactivation of the proteins MAP3K4 and CBP in trophoblast stem cells causes them to become hyperinvasive.

In collaboration with Aleix Prat, PhD and Charles Perou, PhD in the UNC Lineberger Comprehensive Cancer Center, the research team made another discovery: an overlap between the gene expression signature of the mutant tissue stem cells properties during EMT and the triple-negative human breast cancer gene signature that's predictive of invasiveness. The same genes were downregulated.

"This significant genetic intersection between tissue stem cells and TNBC has identified previously unrecognized genes that likely contribute to breast cancer metastasis," said Johnson. "This newly identified gene signature is currently being investigated in different models of breast cancer with the goal of developing new therapeutic interventions for the treatment of TNBC."

Other UNC coauthors are Alicia A. Midland, Nancy L. Johnson, Deborah A. Granger, Piotr A. Mieczkowski, and Shawn M. Gomez. Coauthors at the National Institute of Environmental Health Sciences are Weichung Huang and Leiping Li.

The research was supported in part by the National Institute of General Medical Sciences, a component of the National Institutes of Health

Source: ScienceDaily

CordLife performs India’s first successful mixed stem cell transplantation

The stem cell banking has once again proved to be a life-saver, this time for a five-year-old boy Moinam from Siliguri. He was detected with ebeta thalassemia at the age of five months and after five years his family has a reason to rejoice, when underwent a successful stem cell transplant. CordLife India, Asia’s largest stem cell bank, had preserved the cord blood of Moinam’s sister and provided it to Moinam at the time of the transplant therapy. CordLife made this announcement today, highlighting the fact that this was India’s first successful mixed stem cell transplant.

The boy had to undergo the painful and elaborate process of blood transfusion and was on medication until stem cell transplant from cord blood and bone marrow gave him a new life. Thalassemia is an inherited blood disorder in which the body produces an abnormal form of haemoglobin, the protein in red blood cells that carries oxygen. The disorder results in excessive destruction of red blood cells and causes severe anaemia that can occur within months after birth. If left untreated, severe anaemia can result in insufficient growth and development, as well as other common physical complications that can lead to a dramatically decreased life-expectancy. 

On 3rd April 2011, the stem cell transplantation was carried out by Dr. Ashish Mukherjee at the Netaji Subhash Cancer Research Institute and this is the first time that a mixed stem cell transplant (cord blood and bone marrow) has been performed in India. The boy is now in recovery phase and is expected to get completely cured as his blood tests have been very heartening.

The MD of CordLife India,  Meghnath Roy Chowdhury said, “It has given our international presence and superior technology in preserving stem cells, the parents approached us to preserve their second child’s cord blood during her birth. We are happy that we have been part of this path breaking transplant case, which has given a new lease of life to the child.”

The medical director of CordLife India, Dr Prosanto Chowdhury elaborated that “When stem cells are needed to treat a life-threatening disease, doctors can effectively predict transplant success by evaluating two factors - HLA compatibility and stem cell count. A transplant unit’s stem cell count in relation to the recipient’s body weight is called the cell dose, and it is the most significant predictor for overall transplant survival. In situations, like haematological malignancies, the clock is ticking and the stem cells are to be procured and transplanted at the earliest, so keeping the stem cells, and using them on as and when required basis, is the key to success. Transplants like these confirm CordLife’s technology and our assurance to parents who bank with us their baby’s cord blood. CordLife has added another feather to its cap in its history of successful transplant cases including treating diseases like cerebral palsy and leukaemia through stem cell transplants”.

“This successful transplant case would further enhance the confidence of the parents and stem cell therapy and cord blood banking would be looked up as a possible measure for treatment against such life threatening diseases” according to Meghnath Roy Chowdhury.

There are about 10,000 thalasaemic children born each year in India, and most of them do not live beyond 10 years of age. Thanks to this revolutionary development in the healthcare industry which will help the nation to fight against the life threatening diseases like thalassemia, leukaemia etc.

 

Source: Pharmabiz

Molecular Templates enters RNAi drug-delivery research collaboration with Alnylam Pharma

 Molecular Templates, Inc., a biopharmaceutical company focused on the discovery and development of a new class of small biologic therapies called Engineered Toxin Bodies (ETB), announced that it has entered into a research collaboration with Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, to evaluate and develop Molecular Templates’ proprietary technology for targeted delivery of RNAi therapies. No financial terms were disclosed.

ETBs represent a new class of biologic therapies evolved from a toxin scaffold that have been engineered with a unique targeting domain and designed for reduced immunogenicity. ETBs retain the predictable pharmacokinetics, mechanism-of-action, ability to induce internalization, and intracellular self-routing capabilities of the parent scaffold. Molecular Templates has created vast libraries of ETBs that can be rapidly screened on functionality where the target may or may not be known a priori. These unique properties allow ETBs to target cell surface or intracellular targets that may be intractable to antibody or small molecule approaches.

“We look forward to working closely with Alnylam, the leader in the RNAi space, to capitalize on some of the unique capabilities of our ETB platform,” said Eric Poma, Ph.D., president and chief executive officer of Molecular Templates. “ETBs represent a new class of targeted biologics that possess active intracellular properties that uniquely positions us to address delivery of RNAi drugs in a target directed manner.”

RNA interference (or RNAi) is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. The discovery of RNAi has been widely acknowledged as a major breakthrough in biology, and the technology was recognized for its potential broad impact in medicine with the award of the 2006 Nobel Prize for Physiology or Medicine. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi has accelerated the understanding of these genes and their related pathways. Additionally, RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause targeted gene silencing.

Molecular Templates is a venture-backed biopharmaceutical company focused on the discovery and development of a new class of targeted biologic therapeutics called Engineered Toxin Bodies (ETB) platform technology.

Source: Pharmabiz

Pfizer’s Revatio receives European approval to treat pulmonary arterial hypertension in children

 Pfizer Inc. announced that Revatio (sildenafil citrate) has been approved by the European Commission for the treatment of paediatric patients aged 1 to 17 years old with pulmonary arterial hypertension. Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.

“Pulmonary arterial hypertension is a rare, devastating disease that can affect children," said Dr. Cara Cassino, vice president, Pfizer Medicines Development Group. “With the approval of Revatio, these young patients now have an important treatment option that may help manage their condition. This approval is another example of our ongoing commitment to rare diseases.”

The approval was based on results of a dose-ranging phase 3 study that evaluated the efficacy and safety of Revatio versus placebo in 234 paediatric patients with primary pulmonary hypertension or pulmonary hypertension associated with congenital heart disease. The primary endpoint was improvement from baseline in exercise capacity as assessed by change in peak volume of oxygen consumption (peak VO2) following 16 weeks of treatment. In children who were deemed developmentally unable to perform the test due to young age or the presence of other conditions, efficacy was assessed using secondary endpoints, including hemodynamics and change in WHO functional class.

Estimated change in peak VO2 in evaluable patients receiving any dose of Revatio was 7.71 per cent (95 per cent confidence interval: -0.19 per cent to 15.60 per cent, P=0.056). Dose-related improvements in pulmonary vascular resistance index (PVRI) and mean pulmonary arterial pressure (mPAP) were observed in patients treated with Revatio, and improvements in cardiac index were observed with all three Revatio groups over placebo. Of 120 patients who were WHO functional class II, III or IV at baseline who received Revatio, 32 improved by one functional class, and one subject improved by two functional classes. Four of the 35 patients in the placebo group improved by one functional class.

The adverse reaction profile seen in this paediatric study was generally consistent with that in adults with pulmonary arterial hypertension taking Revatio. Most adverse events were of mild to moderate severity and were consistent with the known pharmacology of phosphodiesterase-5 inhibitors, the class of medications to which Revatio belongs. The most common adverse reactions observed in patients treated with Revatio were vomiting, cough, pyrexia, nausea, lower abdominal pain, upper abdominal pain and photophobia.

Pulmonary arterial hypertension is a rare, progressive disease characterized by high blood pressure in the pulmonary arteries, leading to heart failure and premature death. Pulmonary arterial hypertension can occur with no known underlying cause, or it can be found in association with other disorders such as connective tissue disease or congenital heart disease.

For paediatric patients, Revatio will be available as an extemporaneously prepared oral suspension compounded from Revatio 20 mg tablets and recommended diluents. Revatio is also available in oral and I.V. formulations for the treatment of adults with pulmonary arterial hypertension.

Revatio was first approved by the European Commission in October 2005 for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease. Revatio is approved for the treatment of paediatric pulmonary arterial hypertension only in the EU, with applications pending in other countries.

Since its initial regulatory approval in 2005, Revatio has been approved and launched in more than 50 countries and has amassed more than 100,000 patient-years of experience.

Source: Pharmabiz

Mylan launches generic version of Percodan tablets

 Mylan Inc. announced that its subsidiary Mylan Pharmaceuticals Inc. has launched Oxycodone and Aspirin tablets USP, 4.8355 mg/325 mg, based on an agreement with licensing partner Coastal Pharmaceuticals. This product is the generic version of Endo Pharmaceuticals' Percodan tablets, a treatment for moderate to severe pain.

Oxycodone and Aspirin tablets had US sales of approximately $6.5 million for the 12 months ending December. 31, 2010, according to IMS Health.

Currently, Mylan has 169 ANDAs pending FDA approval representing $100.7 billion in annual sales, according to IMS Health. Forty-five of these pending ANDAs are potential first-to-file opportunities, representing $25.8 billion in annual brand sales, for the 12 months ending June 30, 2010, according to IMS Health.

Mylan Inc. ranks among the leading generic and specialty pharmaceutical companies in the world and provides products to customers in more than 150 countries and territories. The company maintains one of the industry's broadest and highest quality product portfolios supported by a robust product pipeline; operates one of the world's largest active pharmaceutical ingredient manufacturers; and runs a specialty business focused on respiratory, allergy and psychiatric therapies. 

Source: Pharmabiz

Novartis' pancreatic cancer drug Afinitor receives US FDA approval

Novartis announced that the US Food and Drug Administration (FDA) approved Afinitor (everolimus) tablets for the treatment of progressive neuroendocrine tumours of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. This marks the first approval of a treatment for this patient population in the US in nearly 30 years.

The approval was based on phase III data from the RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumours) trial showing treatment with Afinitor more than doubled the time without tumour growth (median 4.6 to 11.0 months) and reduced the risk of cancer progression by 65% when compared with placebo in patients with advanced pancreatic NET (hazard ratio=0.35 [95% confidence interval (CI), 0.27 to 0.45]; p<0.001). A consistent improvement in progression-free survival was seen with Afinitor in all patient subgroups. The FDA determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumours have not been established.

"The FDA approval of Afinitor represents an important step forward for patients with advanced pancreatic NET," said James Yao, MD, Associate Professor of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. "Patients will now have access to a treatment that has been shown to significantly delay tumour growth and reduce the risk of disease progression."

Approximately 60% of pancreatic NET patients are diagnosed with advanced disease. This means that the cancer has already spread to other parts of the body, and is considered aggressive and difficult to treat. The five-year survival rate for these patients is 27%.

"With this approval, US physicians can now offer their patients with progressive pancreatic NET a new treatment helping to fulfil a critical unmet need," said Hervé Hoppenot, president, Novartis Oncology. "This is the third indication for Afinitor in the US in just over two years, providing further evidence that inhibiting mTOR plays an important role in treating multiple tumour types."

Afinitor targets mTOR, a protein that acts as an important regulator of tumour cell division, blood vessel growth and cell metabolism. Preclinical and clinical data have established the role of mTOR in the development and progression of several types of tumours, including advanced pancreatic NET.

Novartis has submitted marketing applications for everolimus for the treatment of patients with advanced NET of gastrointestinal, lung or pancreatic origin to the European Medicines Agency (EMA) and the Swiss Agency for Therapeutic Products (Swissmedic), and additional regulatory submissions are being reviewed by health authorities worldwide.

Neuroendocrine tumours arise from cells that can produce and secrete a variety of hormones that regulate bodily functions. These tumours can occur anywhere in the body; however, most are found in the pancreas (pancreatic NET), gastrointestinal tract or lungs (carcinoid tumours). Pancreatic NET, also known as islet cell tumours, is a rare type of cancer different from pancreatic exocrine cancer, which is generally referred to as pancreatic cancer. There have been limited treatment options for patients with pancreatic NET.

RADIANT-3 is a phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. The trial examined the efficacy and safety of Afinitor plus best supportive care (BSC) versus placebo plus BSC in 410 patients with advanced, low- or intermediate-grade pancreatic NET. Patients who met the study entry criteria were randomized 1:1 to receive either Afinitor 10 mg once-daily (n=207) or daily placebo (n=203) orally, both in conjunction with BSC.

The primary endpoint of RADIANT-3 is progression-free survival. Secondary endpoints include safety, objective response rate (confirmed according to RECIST), duration of response and overall survival.

Afinitor (everolimus) tablets is approved in the US for the treatment of progressive neuroendocrine tumours of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The FDA determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumours have not been established.

Afinitor is approved in the European Union (EU) for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy and also in the US for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

Afinitor is also approved in the US to treat patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of Afinitor is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been shown. Novartis has submitted marketing applications for everolimus for this use to the European Medicines Agency (EMA) and the Swiss Agency for Therapeutic Products (Swissmedic), and additional regulatory submissions are under way worldwide.

In the EU, everolimus is available in different dosage strengths for the non-oncology patient population under the trade name Certican for the prevention of organ rejection in heart and kidney transplant recipients. In the US, everolimus is available in different dosage strengths under the trade name Zortress for the prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant.

Everolimus is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Source: Pharmabiz

Wednesday, May 4, 2011

Extracting Stem Cells from Fat for Tissue Regeneration

 Stem cells extracted from body fat may pave the way for the development of new regenerative therapies including soft tissue reconstruction following tumor removal or breast mastectomy surgery, the development of tissue-engineered cartilage or bone, and the treatment of cardiovascular disease.

An interdisciplinary team of Queen's University researchers led by Dr. Lauren Flynn, a professor in the Departments of Chemical Engineering and Anatomy and Cell Biology, has been working with stem cells extracted from samples of human fat and is developing new methods in the lab to develop these cells into mature tissue substitutes.

While stem cells extracted from fat cannot be grown into as many different types of cells as embryonic stem cells, they do have a number of advantages.

"The advantages include less ethical controversy, abundant cell availability from discarded tissues from elective surgeries like breast reductions and tummy tucks, and a much reduced possibility for immune rejection when re-implanting cells extracted from a person's own fat," explains Dr. Juares Bianco, a postdoctoral fellow in the Department of Chemical Engineering and the Human Mobility Research Centre (HMRC) who is working in the Flynn lab group.

Sarah Fleming, a Master's candidate in the group, is also working to establish a new method for growing the fat stem cells in the lab using a system that mimics the natural tissue environment found within the body. This work is based on Dr. Flynn's development of a technique for washing away all traces of cells from a sample of body fat, leaving behind a three-dimensional tissue scaffold that she calls "decellularized adipose tissue," or "DAT" for short.

This empty scaffold can then be used for soft tissue reconstruction or as a growing environment for the extracted stem cells. Dr. Flynn's preliminary studies have shown that when the stem cells are grown on the DAT scaffold, they naturally begin to mature into fat cells, suggesting that the engineered growth environment influences the type of cell that the basic stem cells will turn into during the tissue regeneration process.

This research was funded in part by NSERC's Collaborative Research and Training Experience Program (CREATE) and was conducted by researchers in the Human Mobility Research Centre (HMRC). The HMRC is a partnership between Queen's University and Kingston General Hospital and serves as a point of collaboration between the disciplines of medicine, engineering, health sciences, and information technology

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/05/110503133040.htm

Extracting Stem Cells from Fat for Tissue Regeneration

 Stem cells extracted from body fat may pave the way for the development of new regenerative therapies including soft tissue reconstruction following tumor removal or breast mastectomy surgery, the development of tissue-engineered cartilage or bone, and the treatment of cardiovascular disease.

An interdisciplinary team of Queen's University researchers led by Dr. Lauren Flynn, a professor in the Departments of Chemical Engineering and Anatomy and Cell Biology, has been working with stem cells extracted from samples of human fat and is developing new methods in the lab to develop these cells into mature tissue substitutes.

While stem cells extracted from fat cannot be grown into as many different types of cells as embryonic stem cells, they do have a number of advantages.

"The advantages include less ethical controversy, abundant cell availability from discarded tissues from elective surgeries like breast reductions and tummy tucks, and a much reduced possibility for immune rejection when re-implanting cells extracted from a person's own fat," explains Dr. Juares Bianco, a postdoctoral fellow in the Department of Chemical Engineering and the Human Mobility Research Centre (HMRC) who is working in the Flynn lab group.

Sarah Fleming, a Master's candidate in the group, is also working to establish a new method for growing the fat stem cells in the lab using a system that mimics the natural tissue environment found within the body. This work is based on Dr. Flynn's development of a technique for washing away all traces of cells from a sample of body fat, leaving behind a three-dimensional tissue scaffold that she calls "decellularized adipose tissue," or "DAT" for short.

This empty scaffold can then be used for soft tissue reconstruction or as a growing environment for the extracted stem cells. Dr. Flynn's preliminary studies have shown that when the stem cells are grown on the DAT scaffold, they naturally begin to mature into fat cells, suggesting that the engineered growth environment influences the type of cell that the basic stem cells will turn into during the tissue regeneration process.

This research was funded in part by NSERC's Collaborative Research and Training Experience Program (CREATE) and was conducted by researchers in the Human Mobility Research Centre (HMRC). The HMRC is a partnership between Queen's University and Kingston General Hospital and serves as a point of collaboration between the disciplines of medicine, engineering, health sciences, and information technology

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/05/110503133040.htm

Blood Test for Alzheimer's: Study Identifies Procedure That Detects Early Stages

 A new blood test that will diagnose Alzheimer's disease may soon hit the market, thanks to an innovative study from the Research Institute of the McGill University Health Centre (MUHC). Their findings have characterized a unique biochemical diagnosis, which identifies patients with this devastating disorder.

This research, published in the month's issue of the Journal of Alzheimer's Disease, has implications for the millions of sufferers worldwide.

"Until now, there has been no definitive diagnostic tool for Alzheimer's, other than postmortem analysis of brain tissue," says senior author Dr. Vassilios Papadopoulos, director of the MUHC Research Institute. "Our clinical study shows that a non-invasive blood test, based on a biochemical process, may be successfully used to diagnose Alzheimer's at an early stage and differentiate it from other types of dementia."

The biochemistry behind the test

Papadopoulos and colleagues based the Alzheimer's blood test on the production of a brain hormone called dehydroepiandrosterone (DHEA). This hormone is present at high levels in the brain where it has a wide range of biological effects.

The researchers were able to promote the production of DHEA, using a chemical process called oxidation, in blood taken from non-Alzheimer's patients. However, oxidation of blood from Alzheimer's patients did not result in an increase of DHEA.

"There is a clear correlation between the lack of ability to produce DHEA through oxidation in the blood and the degree of cognitive impairment found in Alzheimer's disease," says Papadopoulos. "We demonstrated we could accurately and repetitively detect Alzheimer's disease, with small samples of blood. This test also allowed for differential diagnosis of early stages of Alzheimer's disease, suggesting this can be used as a test to diagnose the disease in its infancy."

Treatment implications

"There are many candidate disease-modifying therapies that target the underlying development of Alzheimer's disease, which are in clinical trials," adds Papadopoulos. "However, the implementation of any therapy is dependant on the reliability of the diagnosis."

Currently the diagnosis of Alzheimer's follows the sequence of family history, information, mental assessment and the physical exam, focusing on neurological signs.

"An accurate, easy and specific non-invasive biochemical test that correlates with clinical findings is vital. We believe our results demonstrate that the DHEA-oxidation blood test can be used to diagnose Alzheimer's at a very early stage and monitor the effect of therapies and the evolution of the disease."

The study was authored by Georges Rammouz, Laurent Lecanu and Vassilios Papadopoulos from the MUHC Research Institute and McGill University; Paul Aisen from the University of California at San Diego.

This work was supported by funds from the National Institutes of Health and Samaritan Pharmaceuticals

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/05/110504095623.htm

Regenerating Nerve Cells: Research Offers Hope in New Treatment for Spinal Cord Injuries

Rutgers researchers have developed an innovative new treatment that could help minimize nerve damage in spinal cord injuries, promote tissue healing and minimize pain.

After a spinal cord injury there is an increased production of a protein (RhoA) that blocks regeneration of nerve cells that carry signals along the spinal cord and prevents the injured tissue from healing.

Scientists at the W.M. Keck Center for Collaborative Neuroscience and Quark Pharmaceuticals Inc. have developed a chemically synthesized siRNA molecule that decreases the production of the RhoA protein when administered to the spine and allows regeneration of the nerve cells.

"It is exciting because this minimally-invasive treatment can selectively target the injured tissue and thereby promote healing and reduce pain," says Martin Grumet, associate director of the Keck Center and senior author of a recent study published in the Journal of Neurotrauma.

The neuropathic pain, also known as phantom pain that occurs as a result of a spinal cord injury is often associated with an increased production of RhoA. When researchers injected the chemically synthesized molecular substance into the spinal cords of laboratory rats with spinal cord injury using a procedure similar to a spinal tap, there was an overall improvement in tissue healing and recovery.

More than 250,000 people in the United States are living with a spinal cord injury and currently there is no way to reverse the damage. No drugs for early treatment of spinal cord injury have been approved in over a decade. Based on this joint research, Quark Pharmaceuticals, Inc now has a drug development program for the treatment of spinal cord injury and neuropathic pain. This new research is supported by grants from the New Jersey Commission for Spinal Cord Research and Quark

Source: ScienceDaily     Weblink: http://www.sciencedaily.com/releases/2011/05/110503143520.htm

ICMR seeks cos to commercialize its two new inventions against cancer, dengue vector

 The Indian Council of Medical Research (ICMR) has developed an anti-neoplastic compound for possible treatment of cancer and an herbal composition against dengue vector. The agency has now launched search for interested companies to commercialise these two compounds.

“Cancer therapy is distributed among three interacting subspecialties. The role of surgeon, the radiation oncologist, and the medical oncologist will continue to evolve as new agents becomes clinically available and a multi-modality approached to cancer becomes the rule. The discovery of biologic agents of potential clinical importance continues at a rapid pace,” according to the ICMR.

In the present invention, a novel bioactive molecule from the skin extract of common 'murrel channa striatus' which possesses potent anti-neoplastic property was isolated and purified for the first time. This novel anti-neoplastic compound is devoid of haemorrhegic, haemolytic and defibrinogenating activity. It has no toxic effects on liver and kidney tissues. The compound which already got an India patent was purified by simple and cheaper methods, ICMR sources said.

In another invention, the ICMR has developed an herbal composition useful as larvicide agent against dengue vector. Larval control using this composition will not only stop transmission chain of the disease but will also eliminate inter-generation circulating viruses across vector mosquito, sources said.

“The simple measure to break man-mosquito contact advised through use of bed nets cannot be effective against day biting dengue vector mosquitoes. Since the virus transmitted is transovarial as well as man to mosquitoes and can be retained in nature through transovarial route across mosquito generations, control of larval mosquito becomes a very pertinent issue in intervening transmission cycle of dengue. At present no specific synthetic or bio-larvicide is available against dengue vectors,” ICMR official said.

The larvicidal agent, which has already been granted an Indian patent, is a natural product of wildly grown desert shrub and the raw material is easily available. The plant can also be grown in laboratory through plant tissue culture. The economic and viable agent is also biodegradable and eco-friendly.

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62685&sid=1

Desirudin superior to enoxaparin in patients with poor kidney function undergoing orthopaedic surgery: Study

 

Desirudin reduced major Venous Thromboembolism (VTE) and post-operative bleeding compared with the standard of care, enoxaparin, in patients with poor kidney function undergoing orthopaedic surgery, according to a poster presented at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) meeting.

Entitled The Impact of Renal Function on Options for Venous Thromboembolism Prophylaxis Following Major Orthopaedic Surgery: Insights from a Randomized Trial, the poster was presented at ATVB’s annual meeting in Chicago on April 29. It was based on a retrospective analysis of the large, randomized trial that served as the pivotal trial in the approval by the Food and Drug Administration of desirudin.

“While we’ve long been concerned about the safety of anticoagulants in patients with poor kidney function, this is the first analysis to report a lack of efficacy with standard heparin therapy in this patient population,” says Michael Kurz, PhD, one of the authors and vice president, Global Medical Affairs of Canyon, desirudin’s manufacturer. “Since this is post-hoc analysis, the findings will need to be investigated further in prospective trials, but our analysis addresses an important issue since nearly two-thirds of these patients had renal impairment.”

The poster said: “VTE inversely correlated with GFR in enoxaparin-treated patients. Desirudin provided consistent VTE prevention irrespective of renal function. There was no difference in major bleeding between groups. However, there appeared to be less post-operative bleeding in desirudin-treated patients with moderate renal impairment compared to enoxaparin-treated patients.”

Desirudin is FDA-approved in the United States for the prevention of Deep Vein Thrombosis (DVT) which may lead to Pulmonary Embolism (PE) in patients undergoing elective hip replacement surgery. It is available in the United States under the trade name Iprivask. Desirudin was the first Direct Thrombin Inhibitor (DTI) approved for DVT prophylaxis in Europe, where it has been on the market for over 10 years under the trade name Revasc.

The study that generated the data for the post-hoc analysis was a randomized, active-controlled, double-blind trial of desirudin 15 mg BID vs. enoxaparin 40 mg QD in patients undergoing elective total hip replacement surgery. Renal function was determined using the Cockcroft-Gault equation to calculate Creatinine Clearance (CrCl) and patients were stratified as having normal renal function (CrCl>60 ml/min) or renal impairment (CrCl<60 ml/min). The primary efficacy endpoint was major VTE defined as the combination of proximal DVT, pulmonary embolism and unexplained death. The primary safety endpoint was post-operative major bleeding defined as a bleeding index of greater than two occurring more than 12 hours after surgery.

Patients with renal impairment were more likely to be female (83 vs. 11%), older (70 vs. 60 years) and lighter weight (70 vs. 81 kg) than were patients with normal renal function. Patients with renal impairment randomized to desirudin had a 56% reduction in major VTE and a 45% reduction in major bleeding compared with patients randomized to enoxaparin.

“Desirudin appears to be a promising alternative anticoagulant for elderly women due to its attractive risk:benefit profile,” said Dawn Bell, PharmD, senior vice president and general manager of Canyon Pharmaceuticals.

Canyon Pharmaceuticals is a privately held specialty biopharmaceutical company focused on delivering innovative therapeutic solutions that target important cellular pathways in thrombosis, tumour growth, and metastasis.

 

Source: Pharmabiz  Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62696&sid=2

Cypress Pharma launches generic Elestat

 Cypress Pharmaceutical, Inc. announced that it has commercially launched Epinastine HCl Ophthalmic Solution, 0.05%, which is AT-rated to Allergan's Elestat (epinastine HCl ophthalmic solution) 0.05%.

As the first company to file an Abbreviated New Drug Application (ANDA) containing a paragraph IV certification for this product, Cypress has been awarded a 180-day period of marketing exclusivity.

Elestat is a registered trademark of Boehringer Ingelheim International GmbH and is licensed to Allergan, Inc.

Cypress Pharmaceutical, Inc., is a specialty pharmaceutical company that develops, markets and distributes generic prescription pharmaceutical products to leading national pharmaceutical wholesalers, chain drug stores, distributors, and other retail merchandisers.

Source: Pharmabiz  Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62698&sid=2

Bangalore India Bio kicks off, K'taka govt announces Rs.67.5 cr venture fund assistance to promote hi-tech areas in biosciences

 The 11th edition of the Bangalore Bio was inaugurated with a slew of announcements from the Karnataka government. These include a Rs.67. 5 crore fund assistance for the development of the sector, Out of this an amount Rs.45 crore ($10 million) is allocated to promote projects in the area of high technology which cover stem cells and regenerative and genetics. The remaining Rs.22.5 crore ($5 million) is for companies to help support technology transfers and commercialize research projects. 


Karnataka chief minister BS Yeddyurappa, inaugurated the 3-day exposition said that all efforts were being made to ensure adequate assistance to the state which accounted for 52 per cent of the core companies in biotechnology and the 5 of the top ten enterprises in the country. 


Some of the efforts to ensure the growth of the sector include a revised Millennium Biotech Policy in 2009, setting up 12 biotech finishing schools which were granted Rs.1 crore each to start the courses. The focus is on creation of high quality, industry ready human resources. Biotech sector was also treated by the state government as a non polluting industry and is eligible as a ‘green’ technology enterprise. 


The government has also awarded the biotech park, Bangalore Helix to the bidder Alexandra which would invest Rs.500 crore to set up phase II of this biotech park that would span over 52 acres. The bidder was also responsible to bring in the investments into the Park from international majors. 


Efforts to rope in public private partnerships to set up biotech parks in Dharwad, Mysore, Mangalore among others. The state positively responded to the promotion of the Knowledge sector which covers biotech and information technology. To create an conducive and industry-friendly environment to woo investments. In this regard it is also setting up an IT BT Centre within Helix which involves companies like Indian Institute of Science, Jawaharlal Nehru Centre for Advanced Research, Institute of Bioinformatics and Applied Biotechnology and Strand Genomics. 


The 11th edition of the annual biotech event took the opportunity to provide 12 BT Finishing Schools with Rs.1 crore and these schools would commence the training from this year. The Finishing Schools include Bangalore’s PESIT, Dayananda Sagar College, Maharani Ammani Coolege for Women, Oxford College, Mysore JSS, Mangalore’s Aloysius College, Tumkur’s Siddaganga institute, Sirsi’s MM Arts and Science College to name a few. 


This year’s event is attracting 800 visitors, 150 foreign visitors and 150 stalls. There is also a multi track conference, trade show, vision 2015 leadership series, CEO conclave, BioQuiz as part of the exposition.

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62715&sid=2

Monday, May 2, 2011

Cells Send Signals Via Membrane Nanotubes

 Most of the body's cells communicate with each other by sending electrical signals through nano-thin membrane tubes. A sensational Norwegian research discovery may help to explain how cells cooperate to develop tissue in the embryo and how wounds heal.

For nearly ten years, researchers have known that cells can "grow" ultra-thin tubes named tunnelling nanotubes (TNTs) between one another. These nanotubes -- the length of two to three cells and just 1/500th the thickness of a human hair -- are connections that develop between nearly all cell types to form a communication channel different from any previously known mechanisms.

In 2010, Dr. Xiang Wang and Professor Hans-Hermann Gerdes -- colleagues at the University of Bergen's Department of Biomedicine -- discovered that electrical signals were being passed through nanotubes from one cell to another at high speed (roughly 1-2 m/sec). Their research receives funding under the Research Council's large-scale research programme Nanotechnology and New Materials (NANOMAT).

The breakthrough

In their key experiment, Dr Wang used fluorescent dye that changes in intensity as the electric potential of the cell membrane changes. When two cells connected by forming a nanotube, he poked into one of them with a microinjection needle to depolarise that cell's membrane potential. This caused the fluorescent indicator on the cell membrane to light up like a firework, and it was soon followed by a similar light display in the cell on the other end of the nanotube.

The breakthrough discovery began with an experiment demonstrating intercellular transmission of electrical signals via nanotubes in 2007. The researchers then carried out similar trials with a number of other cell types, observing similar occurrences.

"We confirmed that this is a common phenomenon between cells," explains Professor Gerdes. "Still, this characteristic is not in every cell type."

The experiment was replicated a number of times to obtain statistically reliable data. The electrophysiology group at the University of Bergen took precise conductivity measurements of the cell systems to determine the strength of the electrical coupling. In autumn 2010 the results were published inProceedings of the National Academy of Sciences (PNAS).

Short lifespan

Intercellular nanotubes are far from permanent. Most of them last only a few minutes. This means the researchers cannot predict where and when the cells will form nanotube connections.

"It is truly painstaking work," says Professor Gerdes. "You may sit there examining cells for hours through a microscope without seeing a single tube. If you are lucky, however, you catch sight of a nanotube being created and can film the event."

To raise the likelihood of finding nanotubes, the researchers developed a micro-matrix consisting of thousands of points and bridges on a plate surface. Smaller than a postage stamp, the plate is covered by a nano-structured material to which the cells adhere. The researchers place one cell onto each point and hope that nanotubes will form along the bridges between the points. The camera is focused on these bridges.

Once the nanotubes have been established, the researchers manipulate the cells at specified times; meanwhile the microscope is programmed to photograph, say, 50 preselected points every five minutes. The team can thus obtain data about many nanotube connections in a short time.

How do cells do this?

Dr. Wang quickly discovered that the mere presence of a nanotube was not sufficient to transmit an electrical signal. There had to be another mechanism involved as well.

Many cells form tiny membrane pores with each other called gap junctions, which are made up of ring-shaped proteins. Back in the 1960s it was discovered that directly adjacent cells could exchange electrical impulses through these gap junctions. What Dr Wang found was that one end of the nanotube was always connected to cells by a gap junctions before it transmitted its electrical impulses.

He also found that in some coupled cells voltage-gated calcium channels were involved in the forwarding of the incoming signals. When the electrical signal being sent through the nanotube reaches the membrane of the receiving cell, the membrane surface is depolarised, opening the calcium channel and allowing calcium -- a vital ion in cell signalling -- to enter.

"In other words," explains Professor Gerdes, "there are two components: a nanotube and a gap junction. The nanotube grows out from one cell and connects to the other cell through a gap junction. Only then can the two cells be coupled electrically."

Controls embryonic cells?

Now the scientists are seeking answers as to why the cells send signals to each other in this way.

"It's quite possible that the discovery of nanotubes will give us new insight into intercellular communication," asserts Professor Gerdes. "The process could explain how cells are coordinated during embryo growth. In that phase cells travel long distances -- yet they demonstrate a kind of collective behaviour, and move together like a flock of birds can."

Nanotubes may also be a factor in explaining cell movement associated with wound healing, since cells move toward a wound in order to close it. We already know that electrical signals are somehow involved in this process; scientists can only speculate as to whether nanotubes are involved here as well, stresses Professor Gerdes.

Perhaps brain cells, too?

In terms of electronic signal processing, the human brain surpasses all other organs. If this same signalling mechanism proves to be present in human brain cells, it could add a new dimension to understanding how the brain functions. Communication channels involving synapses and dendrites that are already identified differ widely from nanotubes.

The Bergen-based neuroscientists see this research as an opportunity to formulate better explanations for phenomena related to consciousness and electrical connections in the brain. In the project "Cell-to-cell communication: Mechanism of tunnelling nanotube formation and function," they are now studying precisely how nanotube mechanisms function in brain cells.

Professor Gerdes is currently conducting research at the European Molecular Biology Laboratory in Heidelberg. By studying the electrical connections in vivo he hopes to figure out how the mechanisms work in live subjects. The results could enhance understanding of diseases that occur when cell mechanisms fail to function properly.

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/04/110429120213.htm

Robotic Surgery Effective for Removing Hard-to-Reach Throat Cancer, Study Suggests

 Robotic surgery has become a mainstream tool for removing an ever-increasing variety of head and neck tumors. Now, a team of head and neck surgeons from Mayo Clinic has found robotic surgery can treat cancer in the narrow, hard-to-reach area beyond the tongue at the top of the voice box. Some patients were able to avoid further treatment with chemotherapy or radiation, and most could resume normal eating and speaking.

"We've known it's useful for tongue base and tonsil cancers, but we wanted to assess its effectiveness in the larynx," says Kerry Olsen, M.D., Mayo Clinic otolaryngologist and senior author of the study that was presented April 29 at the Combined Otolaryngological Spring Meetings in Chicago.

The investigation of transoral robotic surgery (TORS) followed nine patients for up to three years following removal of supraglottic squamous cell carcinoma, which affects the area of the larynx above the vocal cords. Most of the patients had advanced-stage disease. The results showed TORS effectively removed cancer, with "clean," disease-free margins, and was easier to perform than the approach of transoral laser microsurgery via a laryngoscope. The patients also underwent the surgical removal of their adjacent neck nodes at the same operation.

"We were pleased with the cancer outcomes," Dr. Olsen says. "We also found patients had minimal trouble after surgery, in most cases resuming normal eating, swallowing and speaking."

With TORS, the robotic arms that enter the mouth include a thin camera, an arm with a cautery or laser, and an arm with a gripping tool to retract and grasp tissue. The surgeon sits at a console, controlling the instruments and viewing the three-dimensional surgical field on a screen. "The camera improves visibility," Dr. Olsen says. "We also gain the ability to maneuver and see around corners and into tight spaces, and we believe we'll now be able to take out more throat tumors than with traditional approaches of the past."

The new application of TORS comes at the right time, Dr. Olsen notes. Cancers of the tongue and throat are on the rise. Not all patients will be candidates for robotic surgery; its use will depend on the architecture of a patient's throat and neck, along with the type and extent of the tumor. "What we know from this study is that for larynx cancer, we have another effective surgical tool available to us," he says. "We can further tailor the cancer treatment for each patient and provide individualized care."

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/04/110429202243.htm

Researchers Link Alcohol-Dependence Impulsivity to Brain Anomalies

 Researchers already know that alcohol dependence (AD) is strongly associated with impaired impulse control or, more precisely, the inability to choose large, delayed rewards rather than smaller but more immediate rewards. Findings from a study using functional magnetic resonance imaging (fMRI) to investigate the neural basis of impulsive choice among individuals with alcohol use disorders (AUDs) suggest that impulsive choice in AD may be the result of functional anomalies in widely distributed but interconnected brain regions that are involved in cognitive and emotional control.

Results will be published in the July 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Individuals with AD score higher on questionnaires that measure impulsivity -- for example, 'I act without thinking' -- are less able to delay gratification, and are less able to inhibit responses," said Eric D. Claus, a research scientist with The Mind Research Network and first author of the study.

Given that impulsive choice in AUDs has been associated with impairment of frontal cortical systems involved in behavioral control, Claus explained, this study was designed to examine the neural correlates of one specific aspect of impulsivity, the ability to delay immediate gratification and instead choose rewards in the future.

"We investigated this choice process in individuals with alcohol use problems ranging from alcohol abuse to severe AD that required treatment," said Claus. "This is the largest study to date that has investigated the neural correlates of impulsive choice in AD, which enabled us to examine the full range of AUDs instead of only examining extreme group differences."

Claus and his colleagues examined 150 individuals (103 males, 47 females) with various degrees of alcohol use. All of the participants completed a delay discounting task -- during which two options were presented, a small monetary (e.g., $10) reward available immediately or a larger monetary reward (e.g., $30) available in time (e.g., two weeks) -- while undergoing fMRI. Impulsive choice was defined as the selection of the more immediate option.

"We showed two things," said Claus. "We replicated previous research by showing that AUD severity was associated with a greater tendency to discount future rewards. In addition, we showed that when individuals with more severe AUDs did delay gratification, they engaged the insula and supplementary motor area -- regions involved in emotional processing and response conflict -- to a greater degree than individuals with less severe AUDs. In summary, these findings suggest that the dysfunction in these regions is graded and increases as a function of AUD severity, rather than operating as an all-or-none function."

"This work showed that the brains of alcoholics don't behave all that differently from the brains of non-alcoholics during delay discounting but that the alcoholic brain had to work harder when they chose the delayed reward," said Daniel W. Hommer, chief of the Section of Brain Electrophysiology & Imaging at the National Institute on Alcohol Abuse and Alcoholism. "Many different studies have shown similar results, that is, alcoholics have a greater increase in brain blood flow to perform the same task as non-alcoholics."

"The current study suggests that the neural dysfunction underlying impulsive choice seems to increase with AD severity," added Claus. "Now that we know that this neural dysfunction is associated with impulsivity, the next steps are to determine whether this impulsivity predates the onset of AD and whether neural measures of impulsivity can predict who will respond best to particular types of treatment. Further, the particular neural dysfunction that we observed indicates that individuals with more AD may be more impulsive because their brain is aversive to delay gratification, and not because it is rewarding to be impulsive. Clinicians might need to deal directly with the aversion of choosing future benefits over immediate ones."

"The most important thing about this paper is that it leads you to question what people mean by impulsive behavior and how should it be measured," said Hommer. "The field has defined increased discounting of time -- failure to delay gratification -- as a good measure of impulsiveness, but the results reported in this paper say 'Wait a minute, delay discounting does not correspond to what is usually meant by impulsiveness.' Rather, brain activity during a delay discounting task looks more like how the brain responds during conflicted decision-making than it does during rapid, unconflicted choice of a highly valued goal." Hommer added that this sort of debate is important to researchers, forcing them to think more carefully about what they mean by impulsive choice

Source: ScienceDaily   Weblink: http://www.sciencedaily.com/releases/2011/04/110415163521.htm

Investigational Agent Shows Promise in Reducing Spread of Prostate Cancer

A drug developed to treat Ewing's Sarcoma, a rare childhood cancer, may also help prevent human prostate cancer from spreading, as seen in new lab studies say researchers at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center (GUMC).

Published online April 29 in PLoS ONE, the researchers report that if the agent continues to work well in further laboratory and preclinical studies, it may be the first prostate cancer drug specifically designed to stop cancer spread, or metastasis.

"This agent does not kill prostate cancer cells, but limits their ability to spread, which could be hugely beneficial in patients," says the study's lead investigator, Aykut Üren, M.D., an associate professor at Georgetown Lombardi. "This study is an early proof of principle that such an approach might be feasible in the clinic, but we have a lot of work to refine and test the drug."

The agent, YK-4 279, was designed in the GUMC Drug Discovery Program, directed by Milton Brown, M.D., Ph.D., a co-author on the paper. YK-4 279 is also being investigated for the treatment of Ewing's sarcoma and is expected to move quickly into a clinical study. Üren participated in the development of YK-4 279, an effort that was led by Georgetown Lombardi researcher Jeffrey Toretsky, M.D., also a co-author of this study.

Recent research has shown that 40 to 70 percent of prostate cancer cells express novel proteins when normal genes such as ETV1 and ERG break off from a chromosome and fuse in to a new location. These new genes produce proteins that push prostate cancer cells to become more aggressive and spread.

Noting that Ewing's sarcoma is produced by a similar fusion gene, the researchers decided to see if their drug would work in prostate cancer cells.

They applied the agent to prostate cancer cells with chromosomal translocations that expressed either an ERG protein or an ETV1 protein and found that the YK-4 279 did inhibit functions of these proteins, which reduced their motility and invasiveness. Tests in cancer cells that did not have either translocation show the agent had no effect.

The researchers also found that although the male hormone androgen turns on genes involved in progression of prostate cancer, including these fusions genes, the presence or absence of androgen is not necessary for this agent to work.

"That means, if successful, YK-4 279 could work in androgen sensitive prostate cancer cells or in cancer that has become resistant to androgen treatment," Üren says.

He says the agent will likely need to be reformulated for prostate cancer use since the fusion gene that causes the Ewing's sarcoma is similar but not identical to ones in prostate cancer. 

The study was funded by Georgetown Lombardi's Cancer Center Support Grant from the National Cancer Institute, the Children's Cancer Foundation, Go4the Goal, Dani's Foundation, Alex's Lemonade Stand Foundation, Liddy Shriver Sarcoma Initiative, Burroughs Wellcome Clinical Scientist Award in Translational Research, and the National Institutes of Health

Source: ScienceDaily  Weblink: http://www.sciencedaily.com/releases/2011/04/110429202240.htm

System in Brain -- Target of Class of Diabetes Drugs -- Linked to Weight Gain

 University of Cincinnati (UC) researchers have determined why a certain class of diabetes drugs leads to weight gain and have found that the molecular system involved (PPAR-γ found in the brain) is also triggered by consumption of high-fat foods.

The study could lead to the modification of existing diabetes therapies and even dietary recommendations to limit the action of this nuclear receptor in the brain.

The research, led by Randy Seeley, PhD, UC professor and Donald C. Harrison Endowed Chair in Medicine, appears as an advanced online publication May 1, 2011, in the journal Nature Medicine.

PPAR-γ is found in white adipose (fat) tissue where it regulates the production of fat cells. This new research describes an important role for PPAR-γ in the brain.

PPAR-γ is the target of a class of diabetes drugs called TZDs (thiazolidinediones). This class of drugs reduces blood glucose levels but also causes considerable weight gain. That weight gain, Seeley says, makes many patients reluctant to use these therapies particularly since many are already trying to lose weight to improve their diabetes.

Seeley and his team set out to determine whether or not the brain's PPAR-γ system was responsible for the weight gain associated with TZDs. The team also wanted to learn if this system in the brain was activated by a high-fat diet.

To do so, they used animal models to test how the class of drugs interacted with the brain PPAR-γ system. They found that by giving TZD drugs in the same manner that people take them, rats gained weight. This was because the drugs activated PPAR-γ in the brain. Thus, weight gain associated with this class of drugs may not be a result of action of PPAR-γ in fat as had been previously thought, but rather a result of a change in activity in parts of the brain known to regulate appetite.

Seeley's team went on to also show that high-fat diets result in activation of the brain PPAR-γ system. Experiments in which the activity of the brain PPAR-γ system was limited resulted in less weight gain when animals were exposed to a high-fat diet similar to diets of many Americans.

"If you artificially turn on PPAR-γ, you can increase food intake in rats," says Seeley. "If you block these receptors in animals on high-fat diets that make animals obese, animals gain less weight."

In the past, says Seeley, people thought that the production of more fat cells in response to TZD drugs was the cause of the resulting weight gain, but he adds, "Just having more fat cells is not enough to make animals or people fatter. Rather you have to eat more calories than you burn and that is exactly what happens when you turn on the brain PPAR-γ system.

"This work helps us understand the complex relationship between our fat, our appetites and type 2 diabetes."

Fat cells are actually quite protective and act as safe repositories for excess nutrients that cause damage when stored in other tissues like the liver and muscle, says Seeley. "It's when nutrients are stored in these cells that individuals are at increased risk for metabolic diseases such as type 2 diabetes."

This, he says, is why TZDs are effective at lowering glucose. The extra fat cells produced become the storage containers for nutrients that would otherwise be harmful if they are stored in other areas of the body.

"You can think of your fat tissue like a bathtub," Seeley says. "A bathtub is designed to hold water. It's a good place to store it. If you turned on the faucet but didn't have a bathtub, the water would go to other parts of your house and cause water damage."

The same is true for nutrients, says Seeley. "It is better to store them in your fat tissue "bathtub" than to have them go to other parts of your body where they can do more harm."

Seeley says PPAR-γ is a system designed at all levels to help you prepare to eat more and gain weight opening up the possibility that food we eat that can activate PPAR-γ might contribute to increasing rates of obesity.

"It tells your brain to eat more and it tells your fat tissue to add new fat cells to serve as repositories to store those extra calories."

He says the next steps would be to find ways to redesign TZDs so that they retain their important glucose-lowering function but with less access to the brain, thereby limiting weight gain.

In the longer term, Seeley says, it's important to better understand the interaction between the brain's PPAR-γ system and the specific micronutrients we consume from fat, protein and sugar.

"We know that one way to activate PPAR-γ is by exposing cells to fatty acids. If we know which ones activate PPAR-γ, we could find ways to alter diets so as to limit their ability to turn on this system that drives increased food intake, making it easier for people to avoid weight gain."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Co-authors, all from the University of Cincinnati, include Bernadette Grayson, Bailing Li, Emily Matter, Karen Ryan and Stephen Woods

 

Source: ScienceDaily    Weblink: http://www.sciencedaily.com/releases/2011/05/110501183815.htm

Gene therapy shows promise against age-related macular degeneration: Study

 A gene therapy approach using a protein called CD59, or protectin, shows promise in slowing the signs of age-related macular degeneration (AMD), according to a new in vivo study by researchers at Tufts University School of Medicine. Led by senior author Rajendra Kumar-Singh, PhD, the researchers demonstrated for the first time that CD59 delivered by a gene therapy approach significantly reduced the uncontrolled blood vessel growth and cell death typical of AMD, the most common cause of blindness in the elderly. The study was published on April 28 in PLoS ONE.

Activation of the complement system, a part of the immune system, is responsible for slowly killing cells in the back of the eye, leading to AMD. Activation of this system leads to the generation of pores or holes known as 'membrane attack complex' or MAC in cell membranes. CD59 is known to block the formation of MAC.

"CD59 is unstable and hence previous studies using CD59 have had limited success. The gene therapy approach that we developed continuously produces CD59 in the eye and overcomes these barriers, giving us renewed hope that it can be used to fight the progression of AMD and potentially other diseases," said Kumar-Singh.

Kumar-Singh is associate professor in the department of ophthalmology at Tufts University School of Medicine (TUSM) and member of the genetics; neuroscience; and cell, molecular, and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

Kumar-Singh and colleagues delivered CD59 to the eye using a deactivated virus similar to one previously shown to be safe in humans. Using an established mouse model of age-related macular degeneration, they found that eyes treated with CD59 had 62 per cent less uncontrolled blood vessel growth and 52 per cent less MAC than controls.

"Treatment was effective when administered at a very specific location beneath the retina, but importantly, also when it was administered to the center of the eye. This finding is especially encouraging because it would allow for a safer and more convenient route of administration of treatment," said co-first author Siobhan Cashman, PhD, assistant professor in the department of ophthalmology at Tufts University School of Medicine and member of Kumar-Singh's lab.

The current standard treatment for some forms of AMD requires an injection directly into the eye approximately every four weeks. According to Kumar-Singh, gene therapy approaches to treat AMD are especially attractive because they will allow patients to be treated less frequently, reducing patient discomfort and lowering chances of infection and other side effects associated with frequent injections into the eye.

The researchers, including co-first author Kasmir Ramo, BS, research technician, believe that while CD59 has significant potential as a treatment for AMD, the gene therapy approach lends itself for application also in other eye and systemic disorders where low-level activation of complement has been implicated.

"Prior to initiating human clinical trials, we will need to perform extensive preclinical toxicology studies. In order to advance this study to phase I clinical trials, we have formed a partnership with Hemera Biosciences Inc. to raise private venture capital," said Kumar-Singh.

AMD, which results in a loss of sharp, central vision, is the number one cause of visual impairment among Americans age 60 and older. While treatments are available for wet AMD, they do not prevent the progression of dry AMD, the form that affects 90 percent of AMD patients. Kumar-Singh noted, however, that the current study in combination with a previously published study from his laboratory suggests that CD59 may be useful for the treatment of both the dry and wet forms of AMD.

This study was supported by grants from The Ellison Foundation; the National Eye Institute, part of the National Institutes of Health; the Virginia B. Smith Trust and grants to the department of ophthalmology at TUSM from the Lions Eye Foundation and Research to Prevent Blindness.

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level.

Source: Pharmabiz   Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62648&sid=2

ISTA Pharma reports positive phase II trial results of bepotastine besilate nasal spray

 ISTA Pharmaceuticals, Inc. announced positive, topline results from its phase II dose-ranging, environmental clinical trial of bepotastine besilate nasal spray for the treatment of symptoms associated with seasonal allergic rhinitis, the inflammation of the nasal passages caused by allergies. According to the trial findings, each of three concentrations of bepotastine besilate nasal spray showed statistically significant improvements compared to placebo in patients' nasal symptoms following exposure to Mountain Cedar pollen during the peak season for this allergen.

These improvements were seen on day one of therapy and were sustained through the two-week treatment period. Further, safety data demonstrated bepotastine besilate was well-tolerated as a nasal spray, with an adverse event profile similar to placebo and consistent with those observed with bepotastine besilate dosed as a nasal spray in prior clinical trials and with other antihistamine nasal sprays.

“One of the most potent seasonal allergy triggers in the United States, Mountain Cedar pollen produces a very strong allergic reaction in sensitive patients and is an excellent allergen to assess the activity of bepotastine besilate as a nasal spray,” commented Timothy R McNamara, Pharm.D, vice president of Clinical Research and Medical Affairs of ISTA Pharmaceuticals. “We are very pleased that the first US environmental clinical trial conducted by ISTA showed great promise for the use of bepotastine besilate for allergic rhinitis. Importantly, the phase II protocol for this study is substantially similar to those we would anticipate for the design of a pivotal programme.”

Dr McNamara continued, “A next step in the development plan for this drug candidate is to explore clinical study designs for a bepotastine besilate/steroid combination nasal spray and, after completing discussions with the FDA, we plan to initiate a phase II study in Mountain Cedar pollen with our bepotastine besilate/steroid combination nasal spray before the end of 2011. This programme represents an exciting potential expansion of our prescription allergy product line, currently focused on Bepreve (bepotastine besilate ophthalmic solution) 1.5% for the treatment of ocular itching associated with allergic conjunctivitis.”

The phase II trial was a randomized, multi-centre, double-masked, placebo-controlled, dose-ranging, parallel-group environmental trial to evaluate the safety and efficacy of bepotastine besilate, dosed twice daily, in patients presenting with allergic rhinitis caused by Mountain Cedar pollen. 

Following initial screening for evidence of Mountain Cedar pollen allergy, approximately 600 patients in Texas, aged 12 years and older, were treated twice per day with one of three concentrations of bepotastine besilate nasal spray or placebo for two weeks. Patients graded both individual nasal and ocular symptoms on a daily basis. 

Safety was evaluated based on several variables, including adverse events, physical and nasal examinations, vital signs and the mean grades for responses to questions in the validated Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) completed at the beginning and end of the trial. Pharmacokinetic (PK) data on the three concentrations of bepotastine besilate nasal spray were assessed based on blood draws, and electrocardiograms were additionally collected at pre-dose and post-dose from a subset of patients. 

The clinical trial showed all three concentrations of bepotastine besilate nasal spray provided statistically significant improvement compared to placebo in reducing total nasal symptoms. Statistically significant improvements also were seen for all three concentrations compared to placebo in terms of total ocular symptoms. All domains in the RQLQ also showed a statistically significant improvement in quality of life with two of the three bepotastine besilate nasal spray concentrations. 

The PK information collected in the Mountain Cedar trial supported the principle that the systemic bioavailability of bepotastine from nasal sprays approximated dose proportionality. In regard to safety, the total number of adverse events was similar in all treatment groups, with the most common adverse events reported being taste, headache, nasal pain and discomfort, and nosebleed. These adverse events were generally mild. Additionally, no serious drug-related adverse events were observed during the phase II trial. 

ISTA expects to report comprehensive data from the phase II trial at an appropriate, peer-reviewed forum in the near future. 

According to the American Academy of Allergy Asthma & Immunology (AAAAI), approximately 60 million Americans are affected by allergic rhinitis, an inflammation of the nasal passages caused by exposure to certain allergens, such as pollen from trees, grasses and plants, animal dander, feathers, dust mites, and moulds. Allergic rhinitis is characterized by a number of symptoms, including sneezing, nasal congestion, nasal itching and runny nose. The eyes, ears, sinuses and throat also can be affected. Current treatments for allergic rhinitis include antihistamines, mast cell stabilizers, anti-inflammatories, and steroids. Based on data from IMS Health in the US, approximately 46.3 million prescriptions were filled for nasal allergy treatments in 2010, resulting in sales of approximately $2.5 billion. 

Bepotastine besilate is a non-sedating, highly selective antagonist of the histamine H1 receptor. It has a stabilizing effect on mast cells, and it suppresses the migration of eosinophils into inflamed tissues. The compound's primary mechanisms of action suggest that it is a potentially effective treatment for nasal symptoms associated with seasonal allergic rhinitis. 

Bepotastine besilate has been approved in Japan for systemic use in the treatment of allergic rhinitis since 2000 and for urticaria/pruritus since 2002. It is marketed in Japan by Mitsubishi Tanabe Pharma Corporation (formerly Tanabe Seiyaku Co., Ltd.) under the brand name Talion.

Talion was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine besilate. In 2001, Tanabe Seiyaku granted Senju Pharmaceutical Co., Ltd., exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine besilate for ophthalmic use.

In 2006, ISTA licensed the exclusive North American ophthalmic rights to bepotastine besilate from Senju. In 2007, ISTA licensed exclusive North American rights to nasal dosage forms of bepotastine besilate from Tanabe Seiyaku and obtained a future right to negotiate for a North American license to oral dosage forms of bepotastine besilate for allergy treatment. 

ISTA's eye drop formulation of bepotastine besilate, Bepreve (bepotastine besilate ophthalmic solution) 1.5%, was approved by the US Food and Drug Administration (FDA) in September 2009 for the treatment of ocular itching associated with allergic conjunctivitis. ISTA's nasal spray formulations for treatment of nasal symptoms of seasonal allergic rhinitis currently are investigational drugs in clinical studies and have not yet been approved by the FDA. 

ISTA Pharmaceuticals, Inc. is a fast growing and the fourth largest branded prescription eye care business in the United States, with an expanding focus on allergy therapeutics.

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62654&sid=2

ABC acquires assets of LAB Research to strengthens services in immunotoxicology

 Applied Biology Company (ABC), the holding company of CIT Safety & Health Research Laboratories (CIT), a leading player among European preclinical CROs, announces the purchase of substantially all of the assets of LAB Research Inc. (LAB Research), consisting of three facilities located in Canada, Denmark and Hungary.

Through this acquisition, the newly created CIT-LAB group becomes one of the top five preclinical CROs, with consolidated sales of USD 103 million (EUR 74 million) and a staff of 830, spread over five sites in France (Evreux and Saint-Nazaire), Canada (Laval), Denmark (Lille Skensved) and Hungary (Veszprém). The financial details of the agreement were not disclosed.

CIT is an established player in the field of preclinical contract research with more than forty years of experience. The CIT-LAB group looks forward to fulfilling even more of the research outsourcing needs of its clients, especially in North America, thanks to LAB Research’s facilities based in Canada. The Scandinavian and Central Europe facilities are also a key asset since this broader geographical positioning will allow closer support for a larger number of customers, an important advantage for running projects successfully.

“With the acquisition of Lab Research, we seized a major opportunity to create a global player serving the pharmaceutical, biotechnology and chemical industries. At a time when the biggest industry companies are turning to global outsourcing agreements, the new CIT-LAB group will be a partner of choice thanks to its ability to carry out a broader range of studies and to provide scientific synergies between facilities,” said Dr Jean-François Le Bigot, CIT and ABC executive chairman. “LAB Research’s three centres have experienced and dedicated scientific teams and modern facilities. Teams, facilities and implemented procedures meet the highest standards in preclinical R&D. They also offer a high level of ethics in terms of animal use, which was an important issue for us. The three LAB Research facilities provide “general services” in non-clinical safety assessment, and each has its own specialization, such as large animals in Canada, minipigs in Denmark or inhalation and ecotoxicology in Hungary. CIT’s own expertise is in large animals, carcinogenicity, genetic toxicology, reprotoxicology and genomics/biomarkers. Each centre will retain a local management team in order to make sure that our clients can benefit from reactivity and flexibility. We will encourage exchanges and sharing of best practices between facilities in common disciplines. When specific expertise is needed for a project, the client will benefit from an access to the experts and techniques from all sites. Lastly, our new size and cumulative scientific expertise will allow us to set up and validate new technologies more quickly. This is essential, in particular to evaluate the most innovative products.”

Source: Pharmabiz  Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62655&sid=2

Saturday, April 30, 2011

Minimising patent infringement risk before product launch

 A patent is a set of exclusive rights granted by a state (national government) to an inventor or their assignee for a limited period of time in exchange for a public disclosure of an invention. The grant of patent gives specific right to the patent holder or the patentee by means of which the patentee can prevent third parties from making, using, selling or offering for sale or importing the patented product or the product prepared by using the patented process. Grant of patent gives negative rights to the patentee, ie. the right to prevent third parties from exploiting the patented invention.

What is patent infringement?

The word infringement has not been defined anywhere in the Patents Act, 1970, but its meaning can be interpreted from the rights of the patentee. That means that violation of any rights of the patentee is deemed to be infringement in Patent Law. Patent filing is increasing globally as well as in India, as indicated by the data provided in annual report of Indian Patent Office, that in the year 2008-2009, 36,812 patent applications were filed in Indian Patent office which is five per cent higher compared to the year 2007-2008. With an increase in the number of filing patent applications, there is obviously a rise in number of patents that are granted and are in force. With increasing number of patents that are in force, there is less freedom for any company to operate within a given jurisdiction and this ultimately leads to a rise in patent infringement risk. In such scenario, if any company wants to launch a product in a particular market, it is essential to make sure that the launch of such a product is not infringing any third parties’ patent rights as there are chances that the product, or the process to make such product or both product and process to be launched, is already claimed in a valid patent of a third party.

Freedom to operate search

Risk analysis in the form of Freedom to Operate (FTO) search or clearance search is a procedure to assess whether or not the product or process is infringing patent rights of any third party. An FTO analysis is performed by meticulously dissecting the product or process into its fundamental components and then scrutinising each component for any attached IP rights.

Though, it is a good idea to get FTO done when technology is in its early stage, it is safe to cross-check the same before a product launch again as the time period between start of research and launch of the product may be large and during that time, there is a possibility of more patents being granted.

Since patent rights are territorial and specific to jurisdiction, the patent granted in one specific country is valid only in that country. A patent granted in US can be used by anyone in India without any risk of patent infringement, provided the product is not exported to US where there is patent protection for the product. A patent has a limited life of 20 years from date of filing or priority, whichever is earlier, and thereafter, a patent is in public domain and can be used by anyone without risk of patent infringement. This means that if the product has to be launched in India, one has to focus on the patents which are in force in India and are likely to be infringed upon product launch.

How is an FTO search done?

FTO can be performed by a patent searcher who has deep understanding of the subject as well as patent law of the territory where FTO needs to be performed. However, legal opinion on infringement can only be given by an advocate or patent attorney. A person, who is not an advocate, can perform the search, present the results in a desirable format but shall preferably not give a written opinion on legal issues related to infringement,.

FTO search involves thorough patent search in a given jurisdiction and identification of relevant patents. The patent claims, which are likely to be infringed, are mapped on the product or process to be launched. This study gives clear idea on chances of infringing third party’s patent rights. FTO is therefore an informed, reasoned, and calculated best estimate of infringement liability in a given jurisdiction at a given period of time.

Identification of relevant patents

Identification of relevant patents for FTO shall be done very carefully as the final opinion or search report depends solely on it. A patent may lapse and cease to be in force if the applicant does not the pay the renewal fee in time. Even though the patent has expired due to non payment of renewal fee, the applicant has one chance to restore it by paying renewal fee within 18 months from the date the patent ceases to have effect. Therefore, this period has to be considered while checking enforceability and validity of patents.

In European Union member countries, a Supplementary Protection Certificate (SPC) is a sui generis, extension of a patent under a specific, different set of rights. This type of right is available for medicinal products, such as drugs and plant protection products, such as insecticides and herbicides. Thereby, while performing FTO, SPC status shall be taken into account.

Calculating term of patent is vital part of an FTO search. The term of patent in case of international applications filed under the Patent Cooperation Treaty designating India, shall be 20 years from the international filing date accorded under the treaty, and shall be considered while checking validity of patent.

Consequences: Cases-in-point

Patent litigations have also cost millions of dollars to companies in legal expenses and awarded damages due. On October 12, 1990, Eastman Kodak had to pay $909,457,567 to Polaroid in a patent infringement case and almost went bankrupt. Kodak was also forced to shut down its $1.5 billion manufacturing plant, lay off 700 workers and spend nearly $500 million buying back the 16 million cameras it had sold between 1976 and 1985. Damages of $873 million were paid to Polaroid at the end of a prolonged 14-year litigation process which finally ended in 1990. Kodak was out of the instant picture business for 15 years. By way of another example, on April 22, 2005 Medtronic, the world’s largest medical technology company, paid $1.35 billion to settle a patent lawsuit.

As evident from the Bajaj/TVS litigation, the losses related to patent infringement do not necessarily result only from damages granted by courts. TVS was put under great loss due to a temporary injunction issued against the sale of its bike called 'Flame', after pumping large sums of money into product development and launch. The case reiterates the fact that patent infringement assessment must be done at a very preliminary stage such as making plans for product development, devising research programs, product launch plan formulation and so on.

Relevance to Indian pharma industry

Generic pharma companies are trying to match every brand name drug with a copycat version without bothering much about the valid patent rights of third parties. There is a high possibility that patent infringements and incorporation of any patented technology without risk assessment may have fatal consequences. Hence, it is essential for generics drug manufacturers to be aware of the risks, patent liabilities and respective consequences before entering any regulated market. A miscalculation in patent expiry dates of brand name drugs leading to the launch of a generic product would result in a patent infringement suit, thereby costing billions in settlement. The FTO search enables pharma companies to identify the areas of research open to them.

Possible way out

The best way to prevent the risk of infringement is to have a license from the patentee. In September 2003, three pharma companies, Cambridge Antibody Technology, Micromet AG, and Enzon Pharmaceuticals, announced that they had signed a non-exclusive cross-license agreement. In the agreement, all three parties obtained substantial "freedom to operate" under some of each other’s intellectual property, to conduct research and develop a defined number of therapeutic and diagnostic antibody-based products. Agreements of this kind have become common practice in certain sectors, as companies seek to ensure that their products, processes and services do not infringe on the patent rights of others.

If you are planning a new product launch, there may be risk of infringing patents rights of third party/ies. It is good business practice to obtain an opinion of counsel and get thorough FTO search done. This opinion should be obtained before undertaking or continuing any activity that might be considered an infringement. Good FTO analysis and opinion can prevent patent litigation that can be an expensive, uncertain and risky affair, and, as the saying goes, prevention is always better than cure.

Source: Express pharma Weblink: http://www.expresspharmaonline.com/20110430/management03.shtml

Managing risks in the pharma industry

 

With the blurring of geographic boundaries and stringent regulations in many countries India is foraying into, it is time to adopt Enterprise Risk Management for the industry to thrive and stall drug recalls. Richa Kedia, Senior Relationship Manager, and Amit Solanki, Relationship Manager, Marsh India Insurance Brokers list out the areas of growing concern

In the recent past India has emerged as one of the largest hub of contract manufacturing for generics and active pharmaceutical ingredients (APIs), with the largest number of US FDA approved plants outside the US. Initially, this was mainly due to the low manufacturing costs and favourable regulatory environment in the country. However, now it can be observed that most contract research and clinical trials are being outsourced to India, not only because of low costs, but also because of the skill of research scholars and the drug-virgin patient population available here, which help to yield better results.

Given the increased level of activity that India is seeing, the industry is evolving at a rapid rate. PricewaterhouseCoopers (PwC) valued the Indian pharmaceutical industry at $12.6 billion in 2009, and is expecting year-on-year growth of 15 per cent. McKinsey and Company predicts the Indian pharma industry to reach $55 billion in a normal scenario or $70 billion in an aggressive growth rate scenario by 2020.

One of the key enablers for this growth was India's adoption of the WTO patent regime in 2005 which was aimed at encouraging product patents in India. Hence, we saw R&D activity on new drugs gathering momentum. Some major Indian pharma firms applied for licenses to conduct clinical trials on at least 12 new drugs in 2010, clearly indicating growing interest in new drug discovery research.

Today, Indian companies are increasingly reaching out to new and emerging markets. The US has always been an important market for the pharma industry, with stringent regulations and lucrative returns. The European Union closely follows suit, and Japan is now emerging as another favourite. According to AV Appaji, Executive Director, Pharmaceutical Export Promotion Council (Pharmaexcil) with an increasingly ageing population, and emphasis on generic drugs in Japan, the stage seems to be set for at least a 20 per cent increase in exports to the country.

To make inroads into a new markets and develop the latest drugs, Indian companies in the lifesciences segment are scouting for the acquisitions. Sun Pharma's successful acquisition of Taro was one of the important acquisitions in 2010. On hindsight, global firms have also been acquiring Indian companies, the best example of which is Daichi's acquisition of Ranbaxy.

While the industry is seeing amazing growth, there is increasing focus on associated risks such as high compliance standards, government reform and pricing pressures, expiration of key drug patents, marketing practices, mergers and acquisitions, increasing litigations, and supply chain management. Adding to this list are issues like nanotechnology and cyber links.

The dynamic business scenario, blurring geographic boundaries and emerging technologies are making the risk landscape evolve at a never-heard-of pace. Also frequent regulatory changes in different geographies make the industry dynamic and susceptible to its influence. As most Indian companies operate in environments replete with international regulations and litigations, it is all the more critical to understand and change the attitude towards managing such risks. It would demand a specialised level of attention and expertise.

Most important risks

Globally, one of the most important risks that the industry faces, is that of compliance to extremely stringent process standards of Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) and pharmacovigilance. The industry is under the vigilance of multiple regulators that impose high standards, which increases efforts on the part of the industry but also builds up trust of its clients. The industry is still considered as in a need of strong drug standards as per Roger L Williams, Chief Executive Officer, US Pharmacopeia (USP).

In India the companies manufacturing and exporting drugs not only need to adhere to the standards imposed by the state FDA, Indian FDA, DCGI, but also standards set by the FDA of the countries to which the product is being exported. The regime of compliance is becoming stronger as regulators look for greater compliance from the industry given the mounting consumer pressures, and increasing healthcare standards. India is right now an observer to the OECD's working group on GLP and also a member of the OECD Test Guidelines Programme. It is striving to get the status of full membership in the near future so that India's industries need not get their test facility (products) certified from the safety angle by other GLP monitoring authorities, and also do not lose on the trade front.

In the US, product liability litigations also remain a major risk. The pre-emption of product liability cases is a huge issue where state law is distinct from the Federal law, hence the historical defense offered by ‘pre-emption’ can be questioned. Familiarity with the US legal system suggests that questioning of the ‘pre-emption’ defense will continue and take time and money to resolve. Unfortunately, in the short term till such time the legal arguments reach their conclusion, the drug companies can expect defense costs, and possibly damages, to go up in cases of 'failure-to-warn,' since they now have to make drug warnings compliant across 50 states.

The pharma generic companies will have to monitor the results of adverse impacts and conduct safety studies on any drug they sell and may require additional safety and efficacy testing. This would push up the costs significantly. Consideration would also have to be given to investing in creating procedures that will allow the monitoring of drug-related laws across all US states.

Another key issue is in the area of supply chain management, forcing most companies to consider alternate suppliers for sourcing raw materials. Which means to source as per the needs, factoring in the external issues.

Last year the industry saw several product recalls due to tightening of norms and audits by the US FDA. The US FDA also recently announced that it would implement stricter outsourcing standards wherein each company would be required to physically audit their suppliers and ensure the quality of drug ingredients, and hence improve safety laying stress on quality. Such audits must be conducted using adequate detailed written procedures by appropriately trained individuals.

With such strict norms, the risk of recall has also increased manifold. Thus every pharma company has been faced with a recall in the past two years - 2009-2010. This if handled inadequately can be highly detrimental to a company's brand and reputation. For instances like this recall preparedness should include not only having a robust recall plan in place, but also training the recall team and testing its effectiveness with mock recalls.

Some of the recalls as listed by www.drugrecalls.com were:

  • Propofol had been ordered to pay over $500 million in fines and penalties ordered by the FDA due to contamination by particulates, which could impede blood flow, causing stroke, kidney failure, and heart attack.
  • McNeil Consumer Healthcare/Johnson & Johnson initiated their sixth recall of 2010, recalling one lot of Tylenol 8-Hour caplets-not impacting the consumers, but at the wholesale level itself.
  • Another Johnson and Johnson recall involved certain lots of rolaids multi-symptom berry tablets. This was initiated to update labeling the product-again not impacting consumers.
  • Johnson & Johnson had another recall for Rolaids Softchews on December 9; Tylenol Cold Liquid products on November 24,2010; Children's Benadryl Allergy Fastmelt Tablets on November 15, 2010; Junior Strength Motrin on November 15,2010, Rolaids Extra Strength Softchews on November 15,2010;
  • FDA requested the withdrawal of Darvon and Darvocet, popular painkillers from the US market due to a new study linking the active ingredient, known generically as propoxyphene, to serious and sometimes fatal heart rhythm abnormalities or heart arrhythmia.

Of the various areas in lifesciences, clinical trials remain the most heavily regulated especially when it is being carried across several countries. The number of clinical trials conducted in India is on the rise and so is the number of serious adverse events.

During April 2009-March 2010, DCGI granted 237 permissions for global clinical trials in the country and as per official records, 462 deaths of clinical trial subjects were reported during the year (2009-10), related or not related to the trial.

Typically with respect to clinical trials in India, the insurance and all responsibility of adverse reactions is passed on to the sponsor by the Clinical Research Organisation (CRO) as per the recent directive of the DCGI. However, it makes the CRO directly responsible for any adverse event to patients. This has triggered questions as to whether it is now compulsory for the CRO to buy insurance from an insurer admitted by the regulatory body, Insurance Regulatory and Development Authority (IRDA). As per our understanding the DCGI directive does not ban agreements between the sponsor and the CMO stating that local insurance covering the trial is taken by the sponsor. It just makes the CRO directly responsible for any adverse reaction. Thus it is not necessary for the CRO/ local Indian entity to take the clinical trials policy themselves, but need to ensure that the policy taken by the sponsor is placed with an admitted insurer in India and that the CRO/local Indian entity is named as an additional insured. It would be more appropriate for CROs to take the clinical trial policy directly and add the sponsor as additional insured though this is not mandatory.

Another area of growing concern is the risk pertaining to environment safety. Associated Press reported in 2009 that drinking water of at least 51 million Americans contains a variety of drugs, including the presence of antibiotics, sedatives, sex hormones and other drugs. Global agencies (WHO/FDA and EU) are now closely monitoring the environmental discharge of the pharmaceutical plants. There are environmental laws that introduce concept of "damage to biodiversity" and itigation lawyers developing new lines of argument around environmental responsibility. The EU's REACH programme and similar regulations by other nations are seeking to ban the use of harmful chemical substances or restrict their use. This is in adherence to the stricter environmental norms which attracts a high cost impact especially to remove drug residue from water.

With new technologies evolving at a rapid pace, the regulatory framework has not able to keep pace. For new technologies like nanotechnology and biosimilars, the risks still need to be identified, managed and disclosed. The regulatory bodies have mostly not even developed a robust testing procedure for nanotechnology drugs and thus the approvals get delayed. More robust quality standards would be required with nanotechnology.

To discuss the risks faced by the pharma industry, Marsh India had organised a Lifesciences Risk Conclave on February 11, 2011 in Mumbai. Under the circumstances the big challenge for the Indian pharma industry when it comes to risk management is to get beyond the point of compliance, and develop an approach to risk management that is supportive of the businesses aims and objectives.

This ensures that the ‘risk’ in opportunity, which is where the profit is, is effectively identified, controlled and managed so that business thrives. Enterprise Risk Management is an approach adopted by many non-ndian lifesciences companies and is viewed as a ‘best practice’. As the lifesciences industry grows in India, the adoption of ‘best practice’, such as Enterprise Risk Management, will allow the industry to manage the evolving risks effectively as it grows.

 Source: Express pharma  Weblink: http://www.expresspharmaonline.com/20110430/management04.shtml

Patients with asthma or allergies initially prescribed montelukast instead of typical first-line therapy have low rates of persistence on montelukast

 

Patients with asthma or allergic rhinitis (nasal allergies), initially prescribed montelukast (Singulair) instead of typical first-line therapy have low rates of persistence on montelukast and may ultimately discontinue therapy altogether, according to a new study presented at the Academy of Managed Care Pharmacy’s 23rd Annual Meeting in Minneapolis, Minnesota. The study will be presented by Prime Therapeutics (Prime), a thought leader in pharmacy benefit management. 

Montelukast is FDA-approved for treatment of asthma and allergic rhinitis. It works by inhibiting leukotrienes, the chemicals that cause inflammation. Montelukast is considered a second line of defence against asthma or allergic rhinitis. Typical first-line therapies are inhaled corticosteroids for asthma and nasal steroids for allergic rhinitis. The inhaled steroids act locally by concentrating their effects directly within the breathing passages, with very few side effects outside of the lungs or sinuses. 

For the study, researchers identified 907 individuals with asthma who filled a claim for newly initiated montelukast therapy in the fourth quarter of 2009. An additional 373 people with allergic rhinitis or allergies who initiated montelukast therapy during the same time period were also identified. Patients were followed for 120 days after their first claim was filled to assess whether they continued to take montelukast after 30, 60, 90 and 120 days. 

At 120 days after initiating montelukast therapy, 30.9 percent of asthma patients still had a supply of this medication. A similar poor persistence on montelukast treatment at 120 days was noted in patients with allergic rhinitis. In addition, at 120 days after montelukast was initiated, the vast majority of asthma and allergic rhinitis patients were lacking any therapy (62.6 and 64.9 percent, respectively). 

“Continued drug treatment is essential for managing asthma,” said Patrick Gleason, PharmD, director of Clinical Outcomes Assessment at Prime. “This study suggests that utilization management programmes may be warranted to ensure that patients who start on montelukast have tried other first-line medications. Making sure patients take recommended medications first will help a greater number of patients manage their illness and will help save costs.”

Prime Therapeutics is a pharmacy benefit management company dedicated to providing innovative, clinically-based, cost-effective pharmacy solutions for clients and members.

 

Source: Pharmabiz        Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62619&sid=2

Unigene completes patient enrolment in oral PTH phase II study to treat osteoporosis in postmenopausal women

 

Unigene Laboratories, Inc. a leader in the design, delivery, manufacture and development of peptide-based therapeutics announced that the company has completed patient enrollment of its phase II study with an experimental oral Parathyroid Hormone (PTH) analogue for the treatment of osteoporosis in post-menopausal women. Unigene is developing its oral PTH in collaboration with GlaxoSmithKline (GSK) as part of an exclusive worldwide licensing agreement. According to the agreement with GSK, Unigene will receive a $4M milestone payment for completion of Phase 2 patient enrollment. 

Ashleigh Palmer, president and CEO, Unigene Laboratories Inc., said, “The completion of enrollment in this phase II study with our proprietary oral formulation of the recombinantly produced PTH analogue is a significant development milestone for Unigene. We are thrilled to have achieved this goal and remain focused on advancing this program that we believe has the potential to address an important medical need.” Palmer continued, “I am extremely impressed with the Unigene team's execution of this study in just four months since the signing of our collaboration with GSK, and believe this not only showcases our clinical trial expertise, but represents an important competitive advantage.”

This multi-centre, double blind with respect to placebo, randomized, repeat dose placebo controlled study will include an open label comparator arm of the Forsteo injectable formulation. The primary endpoint will be an increase in Bone Mineral Density (BMD) at the lumbar spine in subjects at 24 weeks in 93 post-menopausal osteoporotic women following once daily treatment with the orally delivered PTH analogue compared to baseline. Secondary endpoints will evaluate biochemical markers of bone formation and resorption, as well as the safety, tolerability and pharmacokinetics of the oral formulation. 

Osteoporosis is a disease in which bones become brittle and so are more likely to break. In osteoporotic women and men, the density and quality of bone are reduced, leading to deterioration of the skeleton and increased risk of fracture. It's often diagnosed only after an osteoporosis-related fracture happens because prior to such an event, the patient has no outward signs or symptoms. The disease has a significant impact on patients' quality of life and it is estimated that one in three women and one in five men over the age of 50 will develop osteoporosis during their lifetimes. 

The prevalence of osteoporosis is growing as the number of post-menopausal women rises, along with the general increase in life expectancy. Osteoporosis affects an estimated 75 million people in Europe, the US and Japan. In women over 45, osteoporosis accounts for more days spent in hospital than many other diseases, including diabetes, heart attack and breast cancer. There is currently no cure for osteoporosis, but available treatments can strengthen bones and help reduce the risk of fractures. 

On December 10, 2010, Unigene entered into an amended and restated exclusive worldwide license agreement with GSK to develop and commercialize an oral formulation of a recombinantly produced PTH analog for the treatment of osteoporosis in post-menopausal women. Under the terms of the amended and restated agreement, Unigene is responsible for the manufacture of the PTH and the conduct of the phase II study. The company received an upfront payment of $4M to cover costs associated with the phase II study, and will also receive an additional $4M payment upon completion of phase II patient enrollment, as well as further payments of up to $142M based on the achievement of regulatory and commercialization milestones. In addition, Unigene is eligible to receive tiered double-digit royalties in the low-to-mid teens on global sales. Once the Phase 2 study has been completed and based on a review of the data, GSK may elect to assume responsibility for all future development and commercialization of the product. 

Unigene Laboratories, Inc. is a leader in the design, delivery, manufacture and development of peptide-based therapeutics.

 

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62620&sid=2

US FDA approves Zytiga to treat metastatic prostate cancer

 

Centocor Ortho Biotech Inc. announced that the US Food and Drug Administration (FDA) has approved Zytiga (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of men with metastatic Castration-Resistant Prostate Cancer who have received prior chemotherapy containing docetaxel.

Androgens are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can help fuel the tumour’s growth. Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumour tissue is an additional source of androgens. Zytiga is an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources. 

“This FDA approval represents a welcome new option in the treatment of metastatic prostate cancer,” said Howard Scher, MD, Chief of the Genitourinary Oncology Service, Sidney Kimmel Centre for Urologic and Prostate Cancers at Memorial Sloan-Kettering, and one of the co-lead investigators for the phase III clinical study. “As a clinician, I believe the efficacy and safety profile of abiraterone acetate, as well as its oral, once-daily formulation, will help address the important need for additional therapeutic choices for men living with this serious disease.”

“In a phase III study, treatment with Zytiga plus prednisone showed a significant increase in median survival compared with placebo plus prednisone,” said Professor Johann S de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, and one of the co-lead investigators for the phase III clinical study. “It’s an exciting time for men with prostate cancer, and I believe that Zytiga will play an essential role in clinical practice.”

Results of the pivotal phase III, randomized, placebo-controlled, multi-centre study showed that at pre-specified interim analysis, treatment with ZYTIGA in combination with prednisone resulted in a 35 percent reduction in the risk of death (14.8 months vs. 10.9 months [hazard ratio (HR) = 0.646; 95 percent CI: 0.543, 0.768; p<0.0001]) and a 3.9 month difference in median survival compared to placebo plus prednisone. In an updated analysis, results were consistent with those from the interim analysis with a 4.6 month difference between the two arms in median survival (15.8 months vs. 11.2 months [HR = 0.74]).

At a predetermined number of events in the study, an interim analysis was conducted and it was determined that efficacy had been demonstrated. At that time, the study was unblinded at the recommendation of the Independent Data Monitoring Committee.

The most common adverse reactions (greater than or equal to 5 percent) reported in the clinical study were: joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhoea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection.

“Prostate cancer is a significant public health threat in the United States,” said Wendy L Poage, MHA, president, Prostate Conditions Education Council, a national organization committed to men’s health. “Zytiga is an important new option and a welcome addition to the armamentarium we have to fight this deadly disease.”

Zytiga, in combination with prednisone, was evaluated in a phase III, randomized, placebo-controlled, multi-centre clinical study in patients who had received prior chemotherapy containing a taxane (N = 1,195). Patients were randomized 2:1 to receive Zytiga 1 gram daily in combination with prednisone 5 milligrams (mg) twice daily or placebo in combination with prednisone 5 mg twice daily (control arm). 

Zytiga (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic Castration-Resistant Prostate Cancer (CRPC) who have received prior chemotherapy containing docetaxel.

Zytiga may cause fetal harm (Pregnancy Category X) and is contraindicated in women who are or may become pregnant.

Precautions to be taken while hypertension, hypokalemia and fluid retention due to mineralocorticoid excess. Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in hypertension, hypokalemia and fluid retention.  Safety has not been established in patients with LVEF < 50% or NYHA Class III or IV heart failure. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.

Adrenocortical Insufficiency (AI) has been reported in clinical trials after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn or if the patient experiences unusual stress. Perform appropriate tests, if indicated, to confirm AI.  Increased dosages of corticosteroids may be used before, during and after stressful situations.

Hepatotoxicity - Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function and modify, withhold or discontinue Zytiga dosing as recommended.

Food Effect - Zytiga must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. No food should be eaten for at least two hours before the dose of Zytiga is taken and for at least one hour after the dose of Zytiga is taken.

The most common adverse reactions (=5%) reported in clinical trials were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhoea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection.

Zytiga is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6.  Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.

Metastatic castration-resistant prostate cancer or CRPC occurs when cancer has metastasized beyond the prostate and disease progresses despite serum testosterone below castrate levels.

The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid. In some cases, cancer of the prostate can grow slowly compared with other cancers. However, depending on factors including characteristics specific to the patient and the tumour, prostate cancer also can grow very quickly and spread widely.

Excluding skin cancer, prostate cancer is the most frequently diagnosed cancer in men in the United States. In 2010, more than 217,000 new cases of prostate cancer were estimated and more than 32,000 men died from the disease.

Zytiga (abiraterone acetate) was developed by Ortho Biotech Oncology Research & Development, a Unit of Cougar Biotechnology, Inc., and will be marketed by Centocor Ortho Biotech Inc. Marketing applications for Zytiga have been filed with other regulatory authorities throughout the world. 

Zytiga is the first oral, once-daily medication indicated for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.

Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology and oncology. Centocor Ortho Biotech Inc. is a member of the Johnson & Johnson Family of Companies.

 

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62628&sid=2

Pfizer announces top-line results of final two pivotal phase 3 trials of tofacitinib in patients with active RA

Pfizer Inc. announced top-line results from the ORAL Standard (A3921064) and ORAL Step (A3921032) phase 3 studies of tofacitinib (development code: CP-690,550), an investigational, novel, oral JAK inhibitor. 

ORAL Standard is a completed twelve-month study in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) and were randomized to receive tofacitinib 5 or 10 mg BID, adalimumab 40 mg subcutaneously every other week or placebo, each of which was added to stable background MTX. 

The ORAL Standard study met all primary endpoints at the 5 and 10 mg BID doses of tofacitinib, showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months. 

ORAL Step is a completed six-month study in patients with moderate-to-severe active RA who had an inadequate response to a TNF inhibitor and were randomized to receive tofacitinib 5 or 10 mg BID or placebo, which were added to stable background MTX. 

The ORAL Step study met all primary endpoints at the 5 and 10 mg BID doses, showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates; in improving physical function, as measured by mean change in HAQ DI; and in reaching DAS28-4(ESR) <2.6, all assessed at three months. 

No new safety signals emerged in the ORAL Standard and ORAL Step studies. The efficacy and safety profile of tofacitinib in these studies remains consistent with that seen previously in the clinical programme. 

A detailed analysis of the ORAL Standard and ORAL Step efficacy and safety data, including secondary endpoints which are not reported here, will be submitted to a future scientific meeting. 

ORAL Standard is a twelve-month study that enrolled 717 patients with moderate-to-severe active RA who had an inadequate response to MTX to receive tofacitinib 5 or 10 mg BID or adalimumab 40 mg subcutaneously every other week or placebo, each of which was added to stable background MTX. Patients who had previously received adalimumab or had an inadequate response to a TNF inhibitor were excluded from participation. Patients were randomized such that at the month-three visit, nonresponding placebo-assigned patients were advanced in a blinded fashion to a predetermined treatment of tofacitinib, 5 or 10 mg BID, for the remainder of the study; at the end of six months, all placebo-assigned patients were advanced to their predetermined tofacitinib treatment assignment in a blinded fashion for the remainder of the study. Those patients assigned to 5 or 10 mg BID tofacitinib or adalimumab 40 mg every other week at the start of study remained on those dose regimens throughout the 12 months of the study. 

ORAL Step is a six-month study that enrolled 399 patients with moderate-to-severe active RA who had an inadequate response to at least one TNF inhibitor to receive tofacitinib 5 or 10 mg BID or placebo added to stable background MTX. Those patients were randomized such that at the month-three visit, placebo-assigned patients were advanced in a blinded fashion to a predetermined treatment of tofacitinib, 5 or 10 mg BID, for the remainder of the study. Those patients assigned to 5 or 10 mg BID tofacitinib at the start of study remained on those dose regimens throughout the six months of the study. 

Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for RA. More than 4,000 RA patients have been treated with tofacitinib in clinical trials to date. Unlike more recent therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach, targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network. 

Pfizer is studying tofacitinib for RA in the phase 3 ORAL (Oral Rheumatoid Arthritis phase 3 TriaLs) programme, which consists of five pivotal trials and a sixth long-term treatment study at more than 350 locations in 35 countries worldwide. ORAL Standard and ORAL Step are the final two pivotal trials in the programme.
 
Pfizer is also studying orally administered tofacitinib in psoriasis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and renal transplant, and topical tofacitinib in both psoriasis and dry eye disease. 

At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals.

 

Source: Pharmabiz      Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62629&sid=2

 

 

Friday, April 29, 2011

Aegerion gets patent for treating diseases associated with Hyperlipidemia & Hypercholesterolemia using lomitapide

 

Aegerion Pharmaceuticals, Inc. an emerging biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat severe lipid disorders, announced the issuance of Patent No. 7,932,268 for lomitapide for “Methods for Treating Disorders or Diseases Associated with Hyperlipidemia and Hypercholesterolemia While Minimizing Side Effects” by the United States Patent and Trademark Office.

The patent relates specifically to the treatment of hyperlipidemia or hypercholesterolemia, including severe hypercholesterolemia, using step-wise, increasing doses of lomitapide. Such dosing regimens are an essential component of Aegerion's development of lomitapide and other MTP inhibitors. The patent extends until August of 2027 and may be eligible for listing in the US Food and Drug Administration Orange Book.  This patent application has been filed broadly in major markets, and is currently pending or issued in other jurisdictions.

“This is an important milestone for Aegerion,” commented Marc D Beer, chief executive officer of Aegerion, “and we are most appreciative of Dr Daniel Radar of the University of Pennsylvania, the inventor of the patent.” Beer continued, “This patent is an important addition to the Aegerion intellectual property portfolio as titrating the doses enables lomitapide to be used at maximum efficacy while maintaining the highest tolerability profile for the patient. It has the potential to extend patent protection on the use of lomitapide to August 2027.”

 

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62611&sid=2

Rwanda, Merck & Qiagen launch Africa’s first comprehensive cervical cancer prevention programme

 The Government of Rwanda, together with Qiagen NV and Merck known as MSD outside the United States and Canada, announced the launch, in Kigali, Rwanda, of a comprehensive national cervical cancer prevention programme that includes vaccination with Gardasil [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] for appropriate girls 12 to 15 years of age and modern molecular diagnostic screening for women between the ages of 35 and 45. 

Rwanda is the first nation in Africa to offer a comprehensive prevention program that incorporates both HPV vaccination and HPV testing. Rwanda has a population of 2.72 million women ages 15 years and older. Cervical cancer ranks as the most frequent cancer in women of all ages in Rwanda. 

“It is our goal to create a comprehensive, coordinated programme that includes HPV vaccination, cancer screening with HPV DNA testing, and treatment in order to address the nation's unmet needs for cervical cancer-related health services,” said Dr Richard Sezibera, Rwanda's Minister of Health. “This vaccination and screening programme brings us one step closer to reaching our goal of protecting the girls and women in our country. We are pleased to have the support of Merck and Qiagen on this important government initiative.”

During the first three years of the national prevention program the Ministry of Health, with the support of Merck, will offer Gardasil to appropriate girls 12 to 15 years of age, while Qiagen's DNA-based molecular diagnostic HPV tests - the digene HC2 HPV DNA Test and the careHPV Test - will be offered to women between the ages of 35 and 45. Qiagen's careHPV test has been designed to reach women where access to medical care is more challenging - the portable testing system can be performed in any health clinic setting by healthcare workers with minimal lab training. 

Merck will provide more than two million doses of Gardasil to the Government of Rwanda at no cost, while Qiagen will provide 250,000 HPV screening tests at no cost along with all necessary equipment and training to successfully perform the tests. Thereafter, the Government of Rwanda will continue routine vaccination of appropriate 12 year old girls, and Merck will provide Gardasil at a discounted access price that is made available for national vaccination programs in GAVI-eligible countries. Similarly, Qiagen will make its HPV tests accessible under a tiered-market pricing structure designed to enable developing countries to establish and maintain the use of HPV testing within national cervical cancer screening and treatment programmes. 

“Over eighty-five percent of cervical cancer cases occur in the world's poorest countries, having an impact on the women affected, their families and their communities,” said Dr Mark Feinberg, chief public health and science officer, Merck Vaccines. “Reducing the incidence of cervical cancer is a very important public health goal. Through this collaboration with the Government of Rwanda, Qiagen and numerous global public health organizations working in the country to introduce HPV vaccination and HPV DNA testing, women and girls in Rwanda will have greater access to a comprehensive cervical cancer prevention program. We hope this initiative by the Government of Rwanda provides a helpful model for other resource-limited countries to consider as they work to develop their own programmes.”

Gardasil is approved in the United States for use in girls and young women 9 through 26 years of age for the prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18. Gardasil is also approved in the United States for use in boys and men ages 9 through 26 years of age for the prevention of anal cancer caused by HPV types 16 and 18, for the prevention of anal dysplasias and precancerous lesions caused by HPV types 6, 11, 16 and 18, and the prevention of genital warts caused by HPV types 6 and 11.

Merck and Qiagen announced plans to launch a collaborative HPV vaccination and HPV screening programme in September 2009 to help prevent cervical cancer. In addition to their own separate initiatives, the two companies committed to jointly provide up to five million doses of Gardasil and 500,000 HPV tests to developing countries at no charge. As the first recipient of this collaborative effort, Rwanda will become the first GAVI-eligible country to implement a comprehensive program involving both HPV vaccination and HPV DNA-based molecular testing to improve access to cervical cancer prevention programs. Qiagen and Merck continue to reach out to select GAVI-eligible countries to explore the feasibility of implementing cervical cancer reduction programmes. 

“Expanding access to HPV testing, regardless of where a woman lives, is a commitment of Qiagen to help reduce the tremendous burden of cervical cancer, particularly in the developing world. Women in Rwanda, and in other countries where our DNA-based molecular diagnostic tests are available, are being screened for prevention of this potentially life-threatening disease with the most modern diagnostic detection technology available,” said Peer Schatz, chief executive officer of Qiagen N.V. “In many countries women are the cornerstone of families and their communities. It is unfortunate that cervical cancer, which effective measures can help to prevent, often strikes women in their prime years of productivity. We are pleased to partner with the Republic of Rwanda and Merck to introduce this comprehensive program that will greatly expand access to HPV testing and vaccination, which together can help reduce the burden of this disease. We believe this program will demonstrate the positive impact that these types of collaborations can have in terms of improving healthcare.”

Gardasil does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Recipients of Gardasil should not discontinue anal cancer screening if it has been recommended by a health care provider. It has not been demonstrated to provide protection against diseases from vaccine and non-vaccine HPV types to which a person has previously been exposed through sexual activity. It is not intended to be used for treatment of active external genital lesions; cervical, vulvar, vaginal and anal cancers; cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, or anal intraepithelial neoplasia. It has not been demonstrated to protect against disease due to HPV types not contained in the vaccine. 

Gardasil is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after its previous dose. Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following vaccination with Gardasil. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion. Gardasil is not recommended for use in pregnant women. 

Merck is pursuing a systematic and thoughtful approach to improve access to Gardasil in the developing world through four key pillars: innovation, partnerships, pricing and implementation. In 2007 at the Clinton Global Initiative, Merck made a pledge to donate at least three million doses of GARDASIL thro Gardasil Access Programme, which is enabling organizations and institutions in eligible lowest income countries to gain operational experience designing and implementing HPV vaccination projects. 

The collaboration between Merck and Qiagen represents a new commitment and approach that is in addition to, and distinct from, the charitable Gardasil Access Programme. Qiagen is working to improve access to cervical cancer screening through its Qiagencares corporate social responsibility programme. Through the Qiagencares programme, Qiagen is developing the rapid, portable careHPV Test for low-resource settings and health clinics in the developing world and has committed to donating 1.5 million HPV tests to developing countries with the aim of expanding access to cervical cancer screening in areas with the highest disease burden. In addition to its donation to Rwanda, Qiagen currently provides HPV tests to programs in China and India.  

Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. 

Qiagen N.V., a Netherlands holding company, is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated bio-molecules visible.

Source: Pharmabiz        Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62612&sid=2

BioAlliance Pharma accelerates its European clinical development of clonidine Lauriad

 

BioAlliance Pharma SA a company dedicated to specialty and orphan pharma products in oncology and supportive care, announced the extension of its ongoing clonidine Lauriad phase II clinical trial in chemoradiation therapy induced oral mucositis in patients with head and neck cancer to Germany and Spain. The expansion of the trial (currently ongoing in France) to two new countries will raise the total number of centers to over 40 and will help accelerate patient recruitment. 

Based on the incidence of chemoradiation therapy induced oral mucositis in this population, BioAlliance Pharma plans to submit an application dossier to the European and US agencies in Q2 2011 to obtain an Orphan Drug designation for clonidine Lauriad. 

“The orphan drug designation will qualify clonidine Lauriad for our “Orphan Oncology” Business Unit, which features breakthrough products for severe and rare cancers. In addition to clonidine Lauriad, this Unit covers various projects including, at clinical stage, Livatag (advanced hepatocellular carcinoma) in phase II and the AMEP biotherapy (invasive metastatic melanoma) in phase I”, comments Judith Greciet, chief operating officer, Operations and R&D of BioAlliance Pharma. 

BioAlliance Pharma second Business Unit “Specialty Pharma” includes both registered Loramyc (oropharyngeal candidiasis in immunocompromised patients) and Setofilm (chemo- and radiotherapy-induced nausea and vomiting), Sitavir (recurrent herpes labialis), which is in registration phase, as well as other earlier projects which will contribute to generating revenues through partnering. 

BioAlliance is dedicated to specialty pharma and orphan products in cancer treatment and in supportive care, with a focus on drug resistance, conceives and develops innovative products, for specialty markets especially in the hospital setting and for orphan or rare diseases.

 

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62613&sid=2

Call for Papers: International Conference on Nanotechnologies and Biomedical Engineering (ICNBME)

 7 - 8 July 2011, Chisinau, Republic of Moldova.
ICNBME-2011 continues the series of International Conferences in the field of nanotechnologies and biomedical engineering. The conference aims at bringing together scientists and engineers dealing with fundamental and applied research for reporting on the latest theoretical developments and applications in the fields involved.

Contributing papers are called in the following areas:

  • Nanotechnologies and Nanomaterials;
  • Micro- and Nano-objects, Nanostructured and highly integrated systems, Biophysics;
  • Plasmonics and Metamaterials;
  • Biomedical Optics and Lasers;
  • Sensors and Transducers;
  • Terahertz spectroscopy;
  • Biomedical Instrumentation and Devices;
  • Health Care Management;
  • Medical Imaging, Image and Signal Processing;
  • Radiation Protection and Dosymetry, Biological Effect of Radiation;
  • Biomedical Engineering Education;
  • Information Technologies for Health Care, Telemedicine and E-Health;
  • Other topics in biomedical engineering.

Submission of Papers
Contributed papers should be subscribed on four-six pages and submitted by e-mail in Microsoft Word format toicnbm@mail.utm.md

Accepted papers will be included in the Conference Proceedings, distributed to the participants at the beginning of the conference.

Deadlines:

  • May 1 st, 2011 - Submission of extended abstracts
  • May 15th, 2011 - Notification of acceptance
  • June 15th, 2011 - Advanced Conference Registration
  • June 20th, 2011 - Hotel/trip reservation
  • July 1th, 2011 --Deadline for Registration Fee refunding
  • July 5-6th, 2011 - Arrival and Registration of Participants
  • July 7th, 2011 - Opening of the Conference
  • July 9 th, 2011 - Social Program
  • July 9-10th, 2011 - Departure of Participants

For further information and registration, please visit:
http://www.icnbme.sibm.md

Source: WORLDPHARMANEWS

Call for Papers: International Conference on Nanotechnologies and Biomedical Engineering (ICNBME)

 7 - 8 July 2011, Chisinau, Republic of Moldova.
ICNBME-2011 continues the series of International Conferences in the field of nanotechnologies and biomedical engineering. The conference aims at bringing together scientists and engineers dealing with fundamental and applied research for reporting on the latest theoretical developments and applications in the fields involved.

Contributing papers are called in the following areas:

  • Nanotechnologies and Nanomaterials;
  • Micro- and Nano-objects, Nanostructured and highly integrated systems, Biophysics;
  • Plasmonics and Metamaterials;
  • Biomedical Optics and Lasers;
  • Sensors and Transducers;
  • Terahertz spectroscopy;
  • Biomedical Instrumentation and Devices;
  • Health Care Management;
  • Medical Imaging, Image and Signal Processing;
  • Radiation Protection and Dosymetry, Biological Effect of Radiation;
  • Biomedical Engineering Education;
  • Information Technologies for Health Care, Telemedicine and E-Health;
  • Other topics in biomedical engineering.

Submission of Papers
Contributed papers should be subscribed on four-six pages and submitted by e-mail in Microsoft Word format toicnbm@mail.utm.md

Accepted papers will be included in the Conference Proceedings, distributed to the participants at the beginning of the conference.

Deadlines:

  • May 1 st, 2011 - Submission of extended abstracts
  • May 15th, 2011 - Notification of acceptance
  • June 15th, 2011 - Advanced Conference Registration
  • June 20th, 2011 - Hotel/trip reservation
  • July 1th, 2011 --Deadline for Registration Fee refunding
  • July 5-6th, 2011 - Arrival and Registration of Participants
  • July 7th, 2011 - Opening of the Conference
  • July 9 th, 2011 - Social Program
  • July 9-10th, 2011 - Departure of Participants

For further information and registration, please visit:
http://www.icnbme.sibm.md

Source: WORLDPHARMANEWS

XIII Annual INFOTEHNA Pharmaceutical Conference

25 - 27 May 2011, Wörthersee/Klagenfurt, Austria.
INFOTEHNA Group, leading provider of Software Solutions for Pharmaceutical Industry, is organizing its traditional (XIII) Annual Pharmaceutical Conference. Event will take place at idyllic alpine lake Woerthersee in southern Austria.

INFOTEHNA's consultants with guest speakers from Agencies and successful pharmaceutical companies will focus on areas of Regulatory Affairs, Research & Development, Quality Assurance and Quality Control.

Pre-conference day - May 25
Pre-conference day will be devided in two workshops: to newcomers INFOTEHNA's software solutions for faster, easier and efficient work with documentation will be presented, along with several case studies. To loyal customers, INFOTEHNA will unveil new functions of our system, some tricks of Submission Management and show demonstration of Training Management Tool. Event organisers will discuss Pharmacovigilance Documentation in electronic system, connection with Regulatory Authorities and much more.

Conference day - May 26
Speakers from successful Pharma companies and Regulatory Agencies will share their experiences and knowledge in 2 Streams:

1) Regulatory Affairs and Pharmacovigilance
2) Quality and Development

In Hands-on corner you will be able to work with INFOTEHNA's system and test its functionalities, consult experts and get answers to any questions concerning the use of INFOTEHNA's solutions.

For further information and registration, please visit:
http://www.infotehna.com/event/373

Source: WORLDPHARMANEWS

Origami: Not just for paper anymore

 While the primary job of DNA in cells is to carry genetic information from one generation to the next, some scientists also see the highly stable and programmable molecule as an ideal building material for nanoscale structures that could be used to deliver drugs, act as biosensors, perform artificial photosynthesis and more. 

Trying to build DNA structures on a large scale was once considered unthinkable. But about five years ago, Caltech computational bioengineer Paul Rothemund laid out a new design strategy called DNA origami: the construction of two-dimensional shapes from a DNA strand folded over on itself and secured by short “staple” strands. Several years later, William Shih’s lab at Harvard Medical School translated this concept to three dimensions, allowing design of complex curved and bent structures that opened new avenues for synthetic biological design at the nanoscale.

A major hurdle to these increasingly complex designs has been automation of the design process. Now a team at MIT, led by biological engineer Mark Bathe, has developed software that makes it easier to predict the three-dimensional shape that will result from a given DNA template. While the software doesn’t fully automate the design process, it makes it considerably easier for designers to create complex 3-D structures, controlling their flexibility and potentially their folding stability.

“We ultimately seek a design tool where you can start with a picture of the complex three-dimensional shape of interest, and the algorithm searches for optimal sequence combinations,” says Bathe, the Samuel A. Goldblith Assistant Professor of Applied Biology. “In order to make this technology for nanoassembly available to the broader community — including biologists, chemists, and materials scientists without expertise in the DNA origami technique — the computational tool needs to be fully automated, with a minimum of human input or intervention.”

Bathe and his colleagues described their new software in the Feb. 25 issue of Nature Methods. In that paper, they also provide a primer on creating DNA origami with collaborator Hendrik Dietz at the Technische Universitaet Muenchen. “One bottleneck for making the technology more broadly useful is that only a small group of specialized researchers are trained in scaffolded DNA origami design,” Bathe says.

Programming DNA

DNA consists of a string of four nucleotide bases known as A, T, G and C, which make the molecule easy to program. According to nature’s rules, A binds only with T, and G only with C. “With DNA, at the small scale, you can program these sequences to self-assemble and fold into a very specific final structure, with separate strands brought together to make larger-scale objects,” Bathe says.

Rothemund’s origami design strategy is based on the idea of getting a long strand of DNA to fold in two dimensions, as if laid on a flat surface. In his first paper outlining the method, he used a viral genome consisting of approximately 8,000 nucleotides to create 2-D stars, triangles and smiley faces.

That single strand of DNA serves as a “scaffold” for the rest of the structure. Hundreds of shorter strands, each about 20 to 40 bases in length, combine with the scaffold to hold it in its final, folded shape.

“DNA is in many ways better suited to self-assembly than proteins, whose physical properties are both difficult to control and sensitive to their environment,” Bathe says. 

Bathe’s new software program interfaces with a software program from Shih’s lab called caDNAno, which allows users to manually create scaffolded DNA origami from a two-dimensional layout. The new program, dubbed CanDo, takes caDNAno’s 2-D blueprint and predicts the ultimate 3-D shape of the design. This resulting shape is often unintuitive, Bathe says, because DNA is a flexible object that twists, bends and stretches as it folds to form a complex 3-D shape. 

According to Rothemund, the CanDo program should allow DNA origami designers to more thoroughly test their DNA structures and tweak them to fold correctly. “While we have been able to design the shape of things, we have had no tools to easily design and analyze the stresses and strains in those shapes or to design them for specific purposes,” he says.

At the molecular-level, stress in the double helix of DNA decreases the folding stability of the structure and introduces local defects, both of which have hampered progress in the scaffolded DNA origami field.

Postdoctoral researcher Do-Nyun Kim and graduate student Matthew Adendorff, both of the Bathe lab, are now furthering CanDo’s capabilities and optimizing the scaffolded DNA origami design process. 

Building nanoscale tools

Once scientists have a reliable way to assemble DNA structures, the next question is what to do with them. One application scientists are excited about is a “DNA carrier” that can transport drugs to specific destinations in the body such as tumors, where the carrier would release the cargo based on a specific chemical signal from the target cancer cell. 

Another possible application of scaffolded DNA origami could help reproduce part of the light-harvesting apparatus of photosynthetic plant cells. Researchers hope to recreate that complex series of about 20 protein subunits, but to do that, components must be held together in specific positions and orientations. That’s where DNA origami could come in. 

“DNA origami enables the nanoscale construction of very precise architectural arrangements. Researchers are exploiting this unique property to pursue a number of applications at the nanoscale, including a synthetic photocell,” Bathe says. “While applications such as this are still quite far off on the horizon, we believe that predictive engineering software tools are essential for progress in this direction.”

Novel applications may also grow out of a new competition being held at Harvard this summer, called BIOMOD. Undergraduate teams from about a dozen schools, including MIT, Harvard and Caltech, will try to design nanoscale biomolecules for robotics, computing and other applications.

In the meantime, Bathe is focusing on further developing CanDo to enable automated DNA origami design. “Once you have an automated computational tool that allows you to design complex shapes in a precise way, I think we’re in a much better position to exploit this technology for interesting applications,” he says.

For DNA origami to have a broad impact, it needs to become routine to simply order up DNA parts to build any configuration you can dream up, Bathe says. He notes: “Once non-specialists can design arbitrary 3-D nanostructures using DNA origami, their imaginations can run free.”

 

Source: MIT news    Weblink: http://web.mit.edu/newsoffice/2011/dna-origami-0427.html

Thursday, April 28, 2011

CPhI innovation awards open for entries

 

Leading events organiser UBM Live has announced details of the eighth edition of the CPhI Innovation Awards and issued a call for entries. Winners of the annual awards, which recognise, celebrate and honour companies that are innovating and breaking new ground in the pharmaceutical industry, will be announced at UBM’s flagship pharma ingredients event, CPhI Worldwide, which is being held this year at Messe Frankfurt, Frankfurt, Germany from October 25-27, along with co-located events ICSE for contract services, clinical trials and packaging; InnoPack for pharmaceutical packaging solutions; BioPh for the biopharma sector and P-MEC Europe for equipment, machinery and technology. 

Entries are being invited from exhibitors across all the events in Frankfurt and entry categories for the 2011 Awards have been expanded, reflecting the new zoned layout of the events. This year, submissions will be accepted from the following areas: APIs, Custom Manufacturing, Intermediates, Excipients/Formulation, Fine Chemicals, Finished Dosage, Contract Services, Drug Delivery Systems and Biopharmaceuticals. The deadline for submissions  July 29, 2011. Details on how to enter can be found at: www.cphi.com/innovation-awards.

“The CPhI Innovation Awards are an extension of our pharma event brands, effectively the industry’s leading events recognising the industry’s leading innovators. The profile of the awards has grown significantly since their inception in 2004 and they now provide our exhibitors with a high profile, global platform with which to showcase their cutting edge developments,” commented Annemieke Timmers, brand director CPhI. “Last year, the Awards attracted a record thirty entries and we hope to build on this further in 2011. The awards will again be judged by our expert panel who will be looking to highlight achievements, ideas, technologies and products of organisations that truly embrace innovative technology and demonstrate tangible long-term benefits to the pharma industry.” 

Comprised of senior personnel from some of the industry’s leading pharma organisations, the judging panel for the Innovation Awards has remained consistent since 2007 and includes Dr Hendrik Baumann - CU Chemie Uetikon, Zoran Buncic – Pliva, Dr Didier Bensoussan - Dr Reddy’s Laboratories (UK) Ltd., Dr Hans-Leonhard Ohrem - Merck KGaA and Dr Andreas Stolle - Saltigo GmbH. Having reviewed the entries, the panel will announce a shortlist of six entries on September 12 , 2011 and these companies will present to the panel in Frankfurt on October 25, with the Gold, Silver and Bronze Award winners being announced at a ceremony that evening. The three runners-up will be recognised with a nominee certificate.

“The Innovation Awards traditionally attract entries from all spheres of the global pharmaceutical industry, from small biotech companies to the pharma majors, and previous winning entries have ranged from ligand production techniques to reactor efficiency enhancements, to the delivery of probiotics to infants through breast milk,” commented Haf Cennydd, brand director ICSE, P-MEC, InnoPack and BioPh. She added, “By introducing an expanded range of submission categories, we expect to see an even greater diversity of entries than in previous years.”

For further information on the 2011 Awards and to submit an entry, visit: www.cphi.com/innovation-awards.

 

Source: Pharmabiz

CPhI innovation awards open for entries

 

Leading events organiser UBM Live has announced details of the eighth edition of the CPhI Innovation Awards and issued a call for entries. Winners of the annual awards, which recognise, celebrate and honour companies that are innovating and breaking new ground in the pharmaceutical industry, will be announced at UBM’s flagship pharma ingredients event, CPhI Worldwide, which is being held this year at Messe Frankfurt, Frankfurt, Germany from October 25-27, along with co-located events ICSE for contract services, clinical trials and packaging; InnoPack for pharmaceutical packaging solutions; BioPh for the biopharma sector and P-MEC Europe for equipment, machinery and technology. 

Entries are being invited from exhibitors across all the events in Frankfurt and entry categories for the 2011 Awards have been expanded, reflecting the new zoned layout of the events. This year, submissions will be accepted from the following areas: APIs, Custom Manufacturing, Intermediates, Excipients/Formulation, Fine Chemicals, Finished Dosage, Contract Services, Drug Delivery Systems and Biopharmaceuticals. The deadline for submissions  July 29, 2011. Details on how to enter can be found at: www.cphi.com/innovation-awards.

“The CPhI Innovation Awards are an extension of our pharma event brands, effectively the industry’s leading events recognising the industry’s leading innovators. The profile of the awards has grown significantly since their inception in 2004 and they now provide our exhibitors with a high profile, global platform with which to showcase their cutting edge developments,” commented Annemieke Timmers, brand director CPhI. “Last year, the Awards attracted a record thirty entries and we hope to build on this further in 2011. The awards will again be judged by our expert panel who will be looking to highlight achievements, ideas, technologies and products of organisations that truly embrace innovative technology and demonstrate tangible long-term benefits to the pharma industry.” 

Comprised of senior personnel from some of the industry’s leading pharma organisations, the judging panel for the Innovation Awards has remained consistent since 2007 and includes Dr Hendrik Baumann - CU Chemie Uetikon, Zoran Buncic – Pliva, Dr Didier Bensoussan - Dr Reddy’s Laboratories (UK) Ltd., Dr Hans-Leonhard Ohrem - Merck KGaA and Dr Andreas Stolle - Saltigo GmbH. Having reviewed the entries, the panel will announce a shortlist of six entries on September 12 , 2011 and these companies will present to the panel in Frankfurt on October 25, with the Gold, Silver and Bronze Award winners being announced at a ceremony that evening. The three runners-up will be recognised with a nominee certificate.

“The Innovation Awards traditionally attract entries from all spheres of the global pharmaceutical industry, from small biotech companies to the pharma majors, and previous winning entries have ranged from ligand production techniques to reactor efficiency enhancements, to the delivery of probiotics to infants through breast milk,” commented Haf Cennydd, brand director ICSE, P-MEC, InnoPack and BioPh. She added, “By introducing an expanded range of submission categories, we expect to see an even greater diversity of entries than in previous years.”

For further information on the 2011 Awards and to submit an entry, visit: www.cphi.com/innovation-awards.

 

Source: Pharmabiz

Genta begins tesetaxel trial in Japan

 

Genta Incorporated announced that the company has initiated a new clinical trial of tesetaxel in Japan as part of a comprehensive new initiative. Tesetaxel, the leading oral taxane in clinical development, will be evaluated over a limited dosing-range as a single agent in patients with advanced cancer. The new trial will be conducted at Kinki University in Osaka, which will enable the next generation of clinical studies in Japan.

Genta has indicated that gastric cancer is a key initial target for registration studies with tesetaxel. While gastric cancer is the fourth most common tumour type on a global basis, its incidence ranks either first or second in most East Asian countries, including Japan, Korea, Taiwan, and China.

“This study’s initiation reflects Genta’s extensive interactions with Japan’s leading investigators and with the Pharmaceuticals and Medical Devices Agency (PMDA), the drug regulatory authority in Japan”, said Dr Loretta M Itri, Genta’s president, Pharmaceutical Development, and chief medical officer. “We anticipate conducting substantial additional work throughout Japan and East Asia as activity in the tesetaxel development programme continues to accelerate.”

Unlike standard taxanes that must be administered intravenously, tesetaxel is a capsule that is taken by mouth. Compared with the standard agents, clinical and preclinical data show that tesetaxel: is active in diseases that are resistant to standard taxanes, it is not associated with serious (occasionally fatal) hypersensitivity reactions, eliminates requirements for premedication (e.g., steroids, antihistamines, etc.), reduces damage to peripheral nerves and offers flexible and convenient dosing for patients.

Genta Incorporated is a biopharmaceutical company with a diversified product portfolio that is focused on delivering innovative products for the treatment of patients with cancer.

 

Source: Pharmabiz      Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62593&sid=2

Motor protein may offer promise in ovarian cancer treatment

 

A motor regulatory protein can block human ovarian tumour growth, leading to eventual cancer cell death and possible new therapies to treat the disease, according to Penn State College of Medicine researchers.

Among US women, an estimated 21,880 new cases and 13,850 deaths occurred in 2010 from epithelial ovarian cancer, one of the most common forms of ovarian cancer and the most lethal gynaecologic cancer in women.

Previously, Kathleen M Mulder, PhD, professor, biochemistry and molecular biology, along with members of her laboratory, learned that km23-1 -- a protein -- is defective in nearly half of all ovarian cancer patients. In the current study, researchers induced over-expression of km23-1 in human ovarian cancer cells placed in mice, causing the cells to produce large amounts of the normal protein.

km23-1 is a subunit of dynein, a motor protein that transports cargo along paths in the cell called microtubules. The dynein motor has many jobs in the cell, including major roles in cell division.

“Although microtubule-binding agents, such as the drug paclitaxel, are being used in the treatment of ovarian cancer, drug resistance has significantly limited their efficacy,” Mulder said. “It is critical to develop novel, targeted therapeutics for ovarian cancer. Motor protein regulatory agents may offer promise for providing improved efficacies with reduced side effects in the treatment of ovarian cancer and other human malignancies.”

Nageswara Pulipati, PhD, postdoctoral fellow in Mulder's lab, said, “We used a method to cause the tumours to express high levels of normal km23-1, but only in the experimental group of mice. Compared to the control group, the tumours were much smaller when km23-1 was over-expressed.”

“The dynein motor protein is needed to transport checkpoint proteins along the microtubules during mitosis. However, when km23-1 levels are high, at least one checkpoint protein, BubR1, is not transferred properly,” said Qunyan Jin, MD, research associate in Mulder's lab.

During the cell division process, several checkpoints exist where specific proteins put a hold on cell division until proper completion of a specific step can be verified. When km23-1 is over-expressed, a checkpoint is stalled during mitosis -- the stage in the cell division process that normally facilitates equal splitting of the chromosomes into two identical groups before the mother cell splits into two daughter cells.

“Normally, if everything is correct at this checkpoint, the cell then goes on to divide,” Mulder said. “However, with the over-expression of km23-1, the checkpoint stays on and cell division does not proceed normally, which leads to a slow cell death.”

Mulder and her lab team will now look at how the over-expression of km23-1 may be mimicked to target km23-1, using nanotechnology to deliver a drug to the cancer cells, and how this approach may possibly be used in humans.

This National Institutes of Health and the Department of Defence supported this work. Also contributing to this research were Xin Liu, Ph.D., Yan Zhao, PhD, Baodong Sun, MD, Manoj K Pandey, PhD, Jonathan P Huber, PhD and Wei Ding, PhD.

 

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62594&sid=2

Karo Bio and Alkem collaborate to develop eprotirome for dyslipidemia

Karo Bio AB (publ) and Alkem Laboratories Ltd have entered into a collaboration and license agreement regarding eprotirome, currently in late-stage clinical testing for dyslipidemia. Karo Bio will grant Alkem rights to commercialize eprotirome in India and certain other countries. Alkem will participate in Karo Bio’s phase III programme for eprotirome by conducting a pivotal clinical study on eprotirome in India.

Karo Bio has entered into a collaboration and license agreement with the Indian pharmaceutical company Alkem Laboratories Ltd (Alkem). Under the agreement, Alkem will receive the exclusive rights to commercialize eprotirome in India and certain other markets in Asia-Pacific and Africa. Karo Bio is entitled to royalty on Alkem’s future sales of eprotirome.

Alkem will conduct a pivotal clinical phase III trial in order to obtain marketing approval of eprotirome in India. The clinical trial will comprise up to 500 patients with primary hyperlipidemia with a high risk for cardiovascular disease, mainly patients with previous cardiovascular events.

Data from the Indian study will be included in Karo Bio’s application for marketing approval of eprotirome for the treatment of high-risk patients with heterozygous familial hypercholesterolemia (HeFH) in the EU. Karo Bio’s phase III programme for HeFH has previously been estimated to be an investment of SEK 400 million. As a consequence of the collaboration with Alkem, Karo Bio estimates that the investment will be reduced by approximately SEK 100 million.

“The benefits with the collaboration are several. Firstly, it represents a substantial financial value, since our investment in eprotirome’s phase III program will decrease from about SEK 400 million to SEK 300 million as a consequence of Alkem conducting one of the studies. Secondly, we secure distribution in the Indian market, as well as in a number of emerging markets. Finally, we facilitate a broadening of the indication scope of eprotirome, by conducting the study in India in patients representing a larger patient population” said Karo Bio’s president and CEO Fredrik Lindgren.

Eprotirome is a novel, liver-selective thyroid hormone receptor agonist for the treatment of dyslipidemia. The thyroid hormone is one of the body’s own ways of regulating lipids in the blood. This effect is exercised in the liver. Eprotirome’s profile is unique. In one single compound, powerful reductions of several independent risk factors for the development of atherosclerotic cardiovascular diseases are combined. Eprotirome has in three clinical phase II trials been demonstrated to, when administered either as monotherapy or on top of ongoing statin or ezetimibe treatments, produce a profound and clinically meaningful lowering of several important risk factors for the development of cardiovascular disease in patients with high blood lipids. The results are very encouraging, since many patients do not reach their treatment goals with current drugs.

Alkem is the 7th largest company in the Indian pharmaceutical market with leadership in anti-infectives, gastro intestinal and pain management segments and also focusing on strengthening its forays in the chronic segments of cardiology and diabetology.

Karo Bio is a pharmaceutical company focused on the research and development of innovative drugs for unmet medical needs.

Source: Pharmabiz   Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62596&sid=2

Marina publishes data on application of DiLA2 delivery technology for systemic delivery of siRNAs

 

Marina Biotech, Inc. a leading RNAi-based drug discovery and development company, announced today the publication of data highlighting the application of their proprietary DiLA2-based delivery technology for systemic administration of siRNAs; this work is described in Molecular Therapy -- a Nature publication.

The manuscript, titled “An Amino Acid-based Amphoteric Liposomal Delivery System for Systemic Administration of siRNA” describes the development of an amphoteric DiLA2 delivery system which enabled efficient knockdown of multiple targets in liver. Marina Biotech has recently entered an exclusive agreement with Debiopharm Group for the development and commercialization of the Company's bladder cancer program which utilizes a DiLA2-based delivery technology. 

“We're pleased to be able to publish these exciting results,” stated Barry Polisky, PhD, chief scientific officer at Marina Biotech Inc. “Delivery remains one of the key challenges in advancing RNAi-based therapeutics into the clinic and the publication of this paper highlights the impact of our DiLA2 technology in demonstrating safe and efficient systemic delivery of siRNAs. Thus far, the chemical space screened in this manuscript represents a relatively small percentage of the DiLA2 compounds that can be evaluated. The DiLA2 platform provides for a vast and chemically diverse library of compounds that can be tailored to meet particular siRNA delivery objectives for the treatment of various diseases. We will continue to develop our understanding of the capabilities of this novel delivery technology.”

One of the DiLA2-based delivery formulations, an amphoteric formulation, when administered systemically, resulted in greater than 80% knockdown of ApoB, TTR, Factor VII and PCSK9 messenger RNA (mRNA) with a single 2 mg/kg dose. The ED50 values for knockdown of these mRNAs ranged from 0.1 to 0.25 mg/kg. The formulation was well tolerated with single and multiple dose regimens. Additionally when stored frozen, DiLA2-based formulations demonstrated physical and chemical stability for greater than one year, a necessary attribute for developing liposomal-based siRNA drug products. 

Marina Biotech is a biotechnology company, focused on the development and commercialization of RNA interference -- (RNAi) and RNA-based therapeutics and currently includes a clinical programme in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programmes -- in hepatocellular carcinoma and bladder cancer.

 

 

Source: Pharmabiz        Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62598&sid=2

 

Tuesday, April 26, 2011

Joint Call for project proposals in the field of Nanomaterials Research

Department of Science and Technology (DST) and the Academy of Finland and launch a joint call 

for proposals, the aim of which is to promote Indo-Finnish cooperation in the field of Nanomaterials 

Research. Other aims of the joint call are to support long-term systematic research collaboration and 

to establish and strengthen research collaboration networks between India and Finland. 

Research Funding

The successful projects will be funded in India by DST and in Finland by the Academy of Finland. 

The joint projects must meet the criteria of the funding agencies. The research projects are funded 

for a maximum of three years. The funding period starts by January 2012. 

Application procedure

The Indian and Finnish co-applicants will develop one joint research plan that will be sent to both 

the DST and Academy of Finland using the forms of each organisation, respectively. The 

applications must include a statement on how the proposed collaboration brings added valued for 

both countries.   

  

The project budget must clearly delineate justified Indian and Finnish costs. The costs of the Indian 

partner must be eligible as per the guidelines of the DST. Accordingly, the costs of the Finish 

partner must be eligible as per the guidelines of the Academy of Finland. Applicants are reminded 

to include sufficient budget for travel between India and Finland to ensure successful collaboration. 

When drawing up their budget, applicants shall take into account that the Finnish partner pays the 

travel expenses of the visiting Indian researcher in Finland as well as his/her accommodation, and 

per diem allowances. Correspondingly, the Indian partner pays the travel expenses in India of the 

Finnish researcher as well as his/her accommodation and per diem allowances. As the joint research 

projects are funded in bilateral mode the researcher mobility between the two countries should be 

balanced. 

Review process and evaluation

The Academy of Finland and DST will each arrange the evaluation of the applications they receive 

according to their own rules, regulations and practices. The Academy of Finland and DST will form 

a mutual understanding on the projects to be funded. The evaluation criteria of the Academy and the 

Department of Science and Technology are:  

- scientific quality and innovativeness of the research plan 

- added value of the Indo-Finnish  research collaboration 

- feasibility of the research plan  

- scientific merits and results of the Finnish and Indian researchers/research teams  

- support for careers of young researchers.  

Applications addressed to the Department of Science and Technology (DST)

The Indian research team applies for funding from the DST in accordance with the DST’s 

guidelines. DST advises applicants to make sure that their cooperation partner is eligible to apply for funding from the Academy of Finland. Please note that the Finnish partner’s signature is 

required in the application addressed to the DST by the Indian partner. 

The Indian researchers can download the proposal formats from websites www.dst.gov.in and 

www.stic-dst.org and submit 6 hard copies (1 original + 5 copies) and 1 digital copy on CD to DST 

not later than 31

st

 May 2011 through proper channel. One advance copy (in single MSword file) is 

also to be sent by e-mail to rajivarc@nic.in.  

Applications addressed to the Academy of Finland

In this call, the full cost model applies to the calculation of the costs of the Finnish research project. The 

costs of the Indian partners are given only in the  research plan. Applications shall be written so as to 

ensure that the Academy’s contribution to funding comes to no more than 80% of the estimated total 

costs of the Finnish project. See guidelines on how to enter the costs in the application form on the 

Academy’s website at www.aka.fi/eng > For researchers > How to apply > Full cost model.  

The application deadline for Academy funding is 31

st

 May 2011 at 16.15. The deadline is nonnegotiable. Applications are drafted at www.aka.fi/eng > For researchers > Log in to online services. 

Log in and select New application > Joint project call: nanomaterials research (Academy of Finland 

and Indian DST). 

Appendices

Obligatory appendices:  

- research plan, no more than 15 pages, including  

•  a clear description of the planned research and research collaboration (distribution of 

work and methods of implementation) and the added value generated by 

collaboration  

•  joint budget including separate budgets for both partners  

•  justification for the funding applied for  

•  description of any researcher training to be carried out within the project  

•  mobility plan that detailing the research projects  national and international mobility 

plans during the funding period, describing the involvement of foreign researchers in 

the project, and explaining other ways in which the project intends to transcend 

international, national, institutional and public/private sector boundaries  

- curriculum vitae for the Finnish applicant, no more than four pages, and curriculum vitae for 

the Indian applicant, no more than four pages  

- lists of publications of the Finnish and the Indian applicant (the number of the publications 

is not limited). Clearly indicate the ten most important publications in both lists of 

publications in terms of the research plan.  

Case-specific appendices:  

- invitation from foreign university or research institute, if the research or part of it will be 

conducted abroad  

- statement by an ethics committee or the Committee on Animal Experimentation (if 

relevant). The ethical aspects shall always be specified in the research plan.  

- statement by the executive director of a Strategic Centre for Science, Technology and 

Innovation, if relevant, confirming that the applicant’s project is affiliated with the Strategic 

Centre and justifying the significance of the project for the Strategic Centre’s operations  

- progress report on all Academy-funded research projects headed by the applicant that have 

not submitted final reports.  Only the requested appendices are appended to the application. The appendices shall be drafted in 

accordance with the Academy’s guidelines, see www.aka.fi/eng > For researchers > How to apply > 

Appendices. The appendices are drafted in the same language as the application and appended to 

the application form in the online services under section “Appendices”. The only exception is the 

Finnish applicant’s curriculum vitae that is appended to the application form under section 

“Personal data/CV”.

DEADLINE : 31ST MAY, 2011      Official notification: http://www.dst.gov.in/whats_new/IndiaFinlandCollaborativeProgramme010411.pdf

US FDA approves Menactra, a vaccine to prevent meningococcal disease in infants and toddlers

 

The US Food and Drug Administration approved the use of Menactra in children as young as 9 months for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. Menactra already is approved for use in people ages 2 through 55 years.

Meningococcal disease is a life-threatening illness caused by bacteria that infect the bloodstream (sepsis) and the lining that surrounds the brain and spinal cord (meningitis). Neisseria meningitidis is a leading cause of meningitis in young children. Even with appropriate antibiotics and intensive care, between 10 per cent and 15 per cent of people who develop meningococcal disease die from the infection. Another 10 per cent to 20 per cent suffer complications such as brain damage or loss of limb or hearing.

Although the rates of meningococcal disease are low in the United States, infants and toddlers are more susceptible to getting this serious illness. Meningococcal disease is particularly dangerous because it progresses rapidly and can cause death within hours. Early symptoms are often difficult to distinguish from influenza and other common illnesses.

“The highest rate of meningococcal disease occurs in children under one year of age. With today’s approval, Menactra can now be used in children as young as 9 months of age to help prevent this potentially life-threatening disease,” said Karen Midthun, MD, director of FDA's Centre for Biologics Evaluation and Research.

The safety of Menactra in children as young as 9 months was evaluated in four clinical studies in which over 3,700 participants received the vaccine. The most common adverse events reported in children who received Menactra at 9 months and 12 months of age were injection-site tenderness and irritability. Occurrence of fever was comparable to other vaccines routinely recommended for young children.

Menactra is given as a two-dose series beginning at 9-months, three months apart; and the study results showed the vaccine produces antibodies in the blood that are protective against the disease.

Menactra was originally approved on Jan. 14, 2005, for use in individuals ages 11 years through 55 years and was approved in October 2007 for children as young as 2 years. Menactra is manufactured by Sanofi Pasteur Inc. of Swiftwater, Pennsylvania.


Source: Pharmabiz       Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62555&sid=2

Venus Remedies completes phase I & II trials of cancer detection molecule, Tumatrek

 

Venus Remedies, a leading research based pharma, has successfully completed phase I & II clinical trial for VRP1620, a cancer detection  molecule. The clinical study has shown excellent results in detection of breast cancer. With this drug detection of breast cancer would be possible even with a simple X-ray using dye and the sensitivity of other detection devices such as coloured doppler, PET would be increased several times.

On the occasion Dr Manu Chaudhary, research director, said, “VRP 1620 (Tumatrek) is a unique and cost effective diagnostic tool for cancer which can also detect malignancy even through X-ray. It can detect cancer at lesser cost and at primary stage itself.” By detection of cancer at early stage it can increase the cure rate. Scientists believe that after phase III trials of this product VRP-1620 may also help in locating proliferation of cancer site. There are lots of opportunities where the usage of this product can be extrapolated for the benefit of humanity.

A team of scientists from Venus Medicines Research Centre (VMRC), R&D wing of the company, were working for past couple of years on a novel peptide VRP 1620, which is highly selective ETB receptor agonist and is involved in selective vasodilation in solid tumours. “Phase III will be completed this year only and product will be ready for market launch in early 2012,” Chaudhary added.

Venus Remedies has completed and submitted the report of phase I & II study on breast cancer patients for VRP 1620 after due permission from IND Committee and DCGI, Government of India. Phase I was conducted at the prestigious Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh to find the maximum tolerable dose. Later phase II clinical study was conducted at multiple institutions throughout India including PGIMER, Chandigarh and Central India Cancer Research Institute, Nagpur, Maharashtra.

This clinical study documented the pharmacokinetic profile and appropriate dose range for the drug. It also described the efficacy for its use as a diagnostic agent for breast cancer. The efficacy was gauged by observing increase in diameter and the corresponding change in resistive index of tumour vessel. An increase of 17.31 per cent in tumour vessel diameter was observed compared to baseline 12-15 minutes after drug administration of VRP-1620 at dose levels 0.8 µg / Kg body weight. Corresponding to this increase in tumour vessel diameter there was a decrease in RI (resistive index) 7.15 per cent. These changes indicate an increase in tumour blood perfusion causing the contrast media to deeply penetrate, creating a better tumour silhouette.

Tolerability of VRP 1620 was also assessed by the investigators and subjects at the end of study treatment period, which showed that the product is well tolerated.

From past two decades Venus Remedies Limited, has worked to discover, develop and commercialise medications to advance the care of patients suffering from life-threatening diseases in areas of met and unmet medical need. Headquartered in Panchkula, India, the company has made huge expansion and made its presence in 6 continents, operations spanning in more than 60 countries, 3 manufacturing facilities, 11 overseas offices, 1 R&D centre and competent staff of more than 1500 experts.

 

Source: Pharmabiz              Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62564&sid=2

 

Suven Life secures 7 product patents in key markets

 Suven Life Sciences has received total 7 product patents from India, Canada, Japan and Eurasia for its new chemical entities (NCEs) for the treatment of disorders associated with neurodegenerative diseases and these patents are valid through 2023, 2024 and 2025.

The company received two patents from Canada (CA 2,618,636 & CA 2,626,646), three from India (243298, 244912, 246200) and each one from Japan (4571507) and Eurasia (1494). The granted claims of the patents include the class of selective 5-HT compounds discovered by Suven and are being developed as therapeutic agents and are useful in the treatment of cognitive impairment associated with neurodegenerative disorders like Alzheimer's disease, attention deficient hyperactivity disorder, (ADHD), Huntington's disease, Parkinson and schizophrenia.

With these new patents, Suven has a total of five granted patents from Canada, 13 from India, 9 from Eurasia and 4 from Japan for the NCEs. These granted patents are exclusive intellectual property of Suven and are achieved through the internal discovery research efforts. Products out of these inventions may be out-licensed at various phases of clinical development like at phase-I or phase-II.

Venkat Jasti, CEO, said, “WE are very pleased by the grant of these patents to Suven for our pipeline of molecules in CNS arena that are being developed for cognitive disorders which has an estimated $30 billion market potential globally.”

The company has 12 internally discovered therapeutic drug candidates currently in pre-clinical stage of development targeting conditions such as ADHD, dementia, depression, Huntington's disease, Parkinson's disease and obesity in addition to developmental candidates SUVN-502 for Alzheimer's disease and schizophrenia.

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62565&sid=2

Lupin signs patent license agreement with Abbott

 Mumbai based pharma major, Lupin Ltd. announced that the company and its subsidiaries, Lupin Pharmaceuticals, Inc., and Lupin Atlantis Holding SA have entered into a license agreement with Abbott Laboratories and Laboratoires Fournier SA for various Abbott licensed patents for Antara (Fenofibrate) capsules. 

The licensed patents include, collectively, US Patent Nos. 4,895,726; 6,074,670; 6,277,405; 6,589,552; 7,037,529; 7,041,319; 6,596,317 and 6,652,881, and any divisionals, continuations, continuations in part, reissues, re-examinations, and extensions thereof.

The company has not disclosed the terms of the patent license agreement.

 

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62566&sid=2

Celsion receives Japanese patent covering ThermoDox technologies

 

Celsion Corporation a leading oncology drug development company, announced that the Japan Patent Office (JPO) has granted the Japanese counterpart of the “Needham” composition of matter patent, “Temperature-Sensitive Liposomal Formulation,” which is issued in various regions around the world, including the US and European Union. Celsion holds a license agreement with Duke University under which the Company received exclusive worldwide rights to the Needham Patent Family, covering products, such as Celsion's phase III product candidate, ThermoDox, which are developed using Duke's temperature sensitive liposome technology.

Celsion sublicensed its rights within Japan to Yakult Honsha Co., Ltd, the company's Japanese development partner for ThermoDox. The new patent, Japan Patent No. 4691253, provides patent protection for 20 years from the international filing date, which was June 9, 1999. Celsion has an additional divisional patent in the Needham Patent Family pending in Japan and continues to pursue various avenues, including patent term extensions, to maximize the company's intellectual property protection in Japan and other territories. 

“This patent, along with the expertise of Yakult Honsha, a leading Japanese pharmaceutical company, provide the resources for making ThermoDox a commercial success in Japan,” said Michael H Tardugno, Celsion's president and CEO. “We continue to pursue a deliberate and comprehensive global intellectual property strategy aimed at maximizing the value of our drug delivery platform.”

ThermoDox is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT Study, ThermoDox is administered intravenously in combination with RFA. Localized mild hyperthermia (39.5 - 42 degrees Celsius) created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumour. 

For primary liver cancer, ThermoDox is being evaluated in a 600 patient global phase III study at 76 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with Radio Frequency Ablation (RFA) when compared to patients who receive RFA alone as the control. The primary endpoint for the study is Progression-Free Survival (PFS) with a secondary confirmatory endpoint of overall survival. A pre-planned, unblinded interim efficacy analysis will be performed by the independent Data Monitoring Committee when enrollment in the HEAT study is complete and 190 PFS events are realized in the study population.

Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumour cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States, approximately 40,000 cases per year in Europe and is rapidly growing worldwide at approximately 700,000 cases per year, due to the high prevalence of Hepatitis B and C in developing countries.

The standard first line treatment for liver cancer is surgical resection of the tumour; however 90% of patients are ineligible for surgery. Radio Frequency Ablation (RFA) has increasingly become the standard of care for non-resectable liver tumours, but the treatment becomes less effective for larger tumours. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer. 

Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumour-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems.

 

Source: Pharmabiz   Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62561&sid=2

Diabetic completes first-ever polar flight of its kind

Former British Royal Air Force pilot Douglas Cairns succeeded in flying his light plane to the North Pole and landing it there this week, overcoming strong headwinds, the failure of his satellite-based navigation system and his diabetes to earn a place in aviation record books. "It was rather surreal and very exhilarating to be at the crown of our Planet Earth with 24 hours of daylight," he said Friday in an Anchorage interview. "I'm delighted to be able to do this kind of thing solo, with diabetes." Cairns, 47, flew from Barrow, the northernmost community in the United States, to the North Pole on Tuesday in a Beechcraft Baron and completed the 1,300-mile flight in eight hours and 20 minutes. He has submitted the time to the World Air Sports Federation for verification as a world speed record for a light, twin-engine piston aircraft. But the submission is largely academic because Cairns believes he is the first pilot to have made the trip in such an aircraft and to land it at the pole -- a claim backed by a spokesman for Guinness World Records. After circling the geographic pole several times, Cairns landed at a nearby Russian ice camp, making him the first to land a twin-engine piston aircraft at the pole. He then flew home back to Barrow in six hours and 20 minutes, aided by strong tailwinds. For part of the journey, he had to navigate using the sun's position in the sky because global positioning satellite equipment becomes unreliable near the North Slope. The flight was one of a series of expeditions Cairns, who helped found an organization called Pilots with Diabetes, has completed to demonstrate ways to overcome limitations imposed by the disease. Diagnosed with Type 1 diabetes in 1989, Cairns was forced to end his RAF flying career and go into finance. But now, five nations allow insulin-treated diabetics to hold private pilots' licenses. One is the United States, which allows diabetics to fly solo so long as they adhere to regular in-flight monitoring of blood-sugar levels, with corrective actions taken if warranted. After U.S. authorities cleared diabetic pilots for flight in 1997, Cairns took to the skies again and has set various speed and distance records. They include the first-ever around-the-world flight by a diabetic pilot in 2003 and a 50-state flight completed in 2010. His North Pole expedition drew much interest in aviation-crazed Alaska. A veteran Alaska pilot, Ron Sheardown, has been on his support team for years. Alaska Airlines and Alaska-based Era Aviation provided hangar space. And Cairns and his plane were filmed for an appearance in a future episode of "Flying Wild Alaska," a Discovery Channel television series about Alaska bush pilots. Next on Cairns' agenda is a planned speed record circumnavigation around the British coastline, a flight he intends to do in about 14 hours. After that? "In the next few years, I would very much like to make a journey down to the South Pole," he said

Scientists Engineer Nanoscale Vaults to Encapsulate 'Nanodisks' for Drug Delivery

There's no question, drugs work in treating disease. But can they work better, and safer? In recent years, researchers have grappled with the challenge of administering therapeutics in a way that boosts their effectiveness by targeting specific cells in the body while minimizing their potential damage to healthy tissue. The development of new methods that use engineered nanomaterials to transport drugs and release them directly into cells holds great potential in this area. And while several such drug-delivery systems -- including some that use dendrimers, liposomes or polyethylene glycol -- have won approval for clinical use, they have been hampered by size limitations and ineffectiveness in accurately targeting tissues. Now, researchers at UCLA have developed a new and potentially far more effective means of targeted drug delivery using nanotechnology. In a study to be published in the May 23 print issue of the journal Small, they demonstrate the ability to package drug-loaded "nanodisks" into vault nanoparticles, naturally occurring nanoscale capsules that have been engineered for therapeutic drug delivery. The study represents the first example of using vaults toward this goal. The UCLA research team was led by Leonard H. Rome and included his colleagues Daniel C. Buehler and Valerie Kickhoefer from the UCLA Department of Biological Chemistry; Daniel B. Toso and Z. Hong Zhou from the UCLA Department of Microbiology, Immunology and Molecular Genetics; and the California NanoSystems Institute (CNSI) at UCLA. Vault nanoparticles are found in the cytoplasm of all mammalian cells and are one of the largest known ribonucleoprotein complexes in the sub-100-nanometer range. A vault is essentially barrel-shaped nanocapsule with a large, hollow interior -- properties that make them ripe for engineering into a drug-delivery vehicles. The ability to encapsulate small-molecule therapeutic compounds into vaults is critical to their development for drug delivery. Recombinant vaults are nonimmunogenic and have undergone significant engineering, including cell-surface receptor targeting and the encapsulation of a wide variety of proteins. "A vault is a naturally occurring protein particle and so it causes no harm to the body," said Rome, CNSI associate director and a professor of biological chemistry. "These vaults release therapeutics slowly, like a strainer, through tiny, tiny holes, which provides great flexibility for drug delivery." The internal cavity of the recombinant vault nanoparticle is large enough to hold hundreds of drugs, and because vaults are the size of small microbes, a vault particle containing drugs can easily be taken up into targeted cells. With the goal of creating a vault capable of encapsulating therapeutic compounds for drug delivery, UCLA doctoral student Daniel Buhler designed a strategy to package another nanoparticle, known as a nanodisk (ND), into the vault's inner cavity, or lumen. "By packaging drug-loaded NDs into the vault lumen, the ND and its contents would be shielded from the external medium," Buehler said. "Moreover, given the large vault interior, it is conceivable that multiple NDs could be packaged, which would considerably increase the localized drug concentration." According to researcher Zhou, a professor of microbiology, immunology and molecular genetics and director of the CNSI's Electron Imaging Center for NanoMachines, electron microscopy and X-ray crystallography studies have revealed that both endogenous and recombinant vaults have a thin protein shell enclosing a large internal volume of about 100,000 cubic nanometers, which could potentially hold hundreds to thousands of small-molecular-weight compounds. "These features make recombinant vaults an attractive target for engineering as a platform for drug delivery," Zhou said. "Our study represents the first example of using vaults toward this goal." "Vaults can have a broad nanosystems application as malleable nanocapsules," Rome added. The recombinant vaults are engineered to encapsulate the highly insoluble and toxic hydrophobic compound all-trans retinoic acid (ATRA) using a vault-binding lipoprotein complex that forms a lipid bilayer nanodisk. The research was supported by the UC Discovery Grant Program, in collaboration with the research team's corporate sponsor, Abraxis Biosciences Inc., and by the Mather's Charitable Foundation and an NIH/NIBIB Award.

Attractive men have long ring fingers: Study

PARIS: The longer a man’s fourth or ring finger is compared to his index finger, the more likely he is to be judged attractive by women, according to a study released Wednesday. The results, published in the British Royal Society’s journal Biological Sciences, unveil intricate links between foetal exposure of males to hormones, the development of certain physical traits, and what turns on the opposite sex. It also adds to a growing body of research – conducted under the banner of evolutionary psychology – suggesting that the drivers of human behaviour are found, more than previously suspected, in “nature” rather than “nurture”. Earlier studies had already shown that the size ratio between the fourth and second fingers, especially of the right hand, is a reliable indicator of the extent a man was exposed to testosterone while still in the womb. The bigger the gap between a longer ring finger and a shorter index, the greater the likely impact of the hormone. For the new study, scientists led by Camille Ferdenzi of the University of Geneva designed an experiment to find out if women are drawn to the telltale signs of high testosterone levels in men – a symmetrical face, a deeper voice, a particular body odour – who have this more “masculine” finger configuration. More than 80 women university students between 18 and 34 looked at pictures of 49 similarly aged men, and were asked to evaluate them for masculinity and attractiveness. Smaller groups of women listened to recordings of the male voices, and smelled samples of their body odour, taken from cotton pads worn under the arm for 24 hours. “The aim was to understand what makes a man attractive,” and whether at least some of those qualities “were in part conditioned by the foetal environment,” Ferdenzi said in an interview. For the visual test, the results were unambiguous. “The longer the ring finger compared to the index – that is, the greater the exposure to testosterone – the more attractive the face was rated,” she said by phone. “We also found that attractiveness and symmetry in the face are highly correlated.” Such a preference might have evolved to boost a female’s chances of reproductive success through mating with a more virile partner, she said. Surprisingly, however, women did not consistently tag the same men as “masculine”. Nor did their preferences for voice or odours correspond to the longer ring-finger males. “There wasn’t any relation between the 2D-4D” – 2nd digit, 4th digit – “ratio and the reactions of the women to odour,” Ferdenzi said. One reason, she speculated, may be that voice and body odour are more dependent on fluctuating levels of adult testosterone than on pre-natal testosterone. The ring-index finger ratio has also proven to be a useful indicator for gauging the risk of prostate cancer, likewise tied to high levels of testosterone. Research published in December showed that the chances of developing the disease drop by a third in men whose index finger is longer than their ring finger. Other studies have also found a link between exposure to hormones before birth and the development of other diseases, including breast cancer and osteoarthritis. Published: April 20, 2011 http://tribune.com.pk/story/153080/attractive-men-have-long-ring-fingers-study

Sunday, April 24, 2011

Maharashtra to include Ayurveda as part of MBBS syllabus

 The  Maharashtra University of Health Science (MUHS) will soon constitute an expert committee to discuss the new syllabus for the MBBS students for the coming academic year as it has been decided to include   basic Ayurveda as part of MBBS syllabus in the medical colleges in the state. 

A decision to include Ayurveda in MBBS syllabus was taken following recommendations from the Ayush department. There are 34 private and government medical colleges in the state. Their syllabus comes under the purview of the MUHS. According to the Ayush recommendations, every medical college should reserve at least 20 hours to teach ayurvedic science in MBBS classes. 

Dr Arun Jamkar, vice chancellor, MUHS said “As per the suggestions made by Dept of Ayush we are meeting up to form a committee to implement these directives and to discuss the new syllabus for the medical students for the coming year.” He further informed that Maharashtra will be the first state for implementing such directives.

Dr Arun Jamkar, vice chancellor, MUHS said “We are meeting soon to form a committee to implement these directives and to discuss the new syllabus for the medical students for the coming year.” 

Dr Vijay Magar, associate professor at the RA Podar Ayurvedic College and Hospital, Mumbai said “Ayurveda is an ancient medicine and the students are more interested in learning modern medicine. For this it is a nice move as modern medicine doctors should be familiar with ancient medicine and its treatment methodology. Every person should know about Ayurveda. Instead of devoting so much time for a course, we can have atleast one lecture every week. Like for conducting research in herbal products there are separate institutes.”

Dr Jamkar informed that as most of the universities across the world has been teaching the ancient medicine of their respective cultures. For instance, modern medicine doctors in China get lessons in Chinese medicine. “Finally we too are introducing the study of our ancient medicine. We are proud that ours will be the first state in the country to implement the Ayush directives”, he added.

MUHS ensures in proper and systematic instruction, teaching, training and research in modern medicine and Indian systems of medicine in the state of Maharashtra, and to have balanced growth in the medical sciences. They are taking initiative to implement this decision to attract more MBBS students to take up Ayurveda as the major subject to practice and to research on the same.

Source: Pharmabiz       Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62514&sid=1

NicOx withdraws MAA for its osteoarthritis candidate naproxcinod in Europe

 NicOx SA announced its decision to withdraw the Marketing Authorization Application (MAA) for its osteoarthritis candidate naproxcinod from the centralized procedure in Europe. NicOx submitted the naproxcinod MAA to the European Medicines Agency (EMA) in December 2009.

The decision to withdraw the European MAA was made following the feedback at the April meeting of the Committee for Medicinal Products for Human Use (CHMP) that the CHMP would not adopt a formal positive opinion on the basis of the submitted information. NicOx has notified the EMA of its decision to withdraw the naproxcinod MAA, based on the CHMP considering that the data provided did not allow them to conclude on a positive benefit-risk balance. NicOx is now evaluating its options for the potential further development of naproxcinod in Europe, together with its advisors and with Grupo Ferrer Internacional SA which has an option for rights to naproxcinod in certain European countries.

NicOx submitted a New Drug Application (NDA) for naproxcinod to the US Food and Drug Administration (FDA) and received a Complete Response Letter in July 2010 stating that the FDA did not approve naproxcinod. NicOx has decided to appeal the FDA decision under the FDA’s Formal Dispute Resolution process and is currently finalizing the submission of the supporting information for the appeal.

NicOx is developing a number of nitric oxide-donating New Molecular Entities (NMEs), both internally and with its partners Bausch + Lomb, Merck (known as MSD outside the United States and Canada) and Ferrer. The company had €107.3 million in cash and cash equivalents as of December 2010 and is focused on a number of strategic priorities, including actively seeking appropriate M&A opportunities and new alliances on existing programs as well as targeting internal research resources on the most promising programmes.

NicOx is a pharmaceutical company focused on the research, development
and future commercialization of drug candidates. It is applying its proprietary nitric oxide-donating R&D platform to develop an internal portfolio of New Molecular Entities (NMEs) for the potential treatment of inflammatory, cardiometabolic and ophthalmological diseases.

 

Source: Pahrmabiz        Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62520&sid=2

Amgen, UCB phase 2 study of AMG 785/CDP7851 in patients with postmenopausal osteoporosis meets primary endpoint

 

Amgen and UCB announced positive top-line results from their phase 2 clinical study comparing sclerostin-antibody AMG 785/CDP7851 to placebo in postmenopausal women with low bone mineral density (BMD) for the treatment of postmenopausal osteoporosis (PMO).

This phase 2 study met its primary endpoint, demonstrating significant increases in lumbar spine bone mineral density at month 12 for the AMG 785/CDP7851 active arms versus the placebo arm. In addition, AMG 785/CDP7851 compared positively with the two active comparators, teriparatide and alendronate.

The overall incidence of adverse events was generally balanced between groups. Consistent with previous studies, injection site reactions were reported more frequently in those patients receiving AMG 785/CDP7851.

"We are very encouraged by the results of this study," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Despite available osteoporosis therapies, there remains a significant need for additional treatment options that form new bone in women with postmenopausal osteoporosis. We look forward to working with UCB to advance the AMG 785/CDP7851 programme into phase 3."

"The AMG 785/CDP7851 project with Amgen is one of the most exciting pipeline programs in UCB's immunology disease portfolio. The favourable comparison with established therapies indicates the potential for a change of treatment paradigms with AMG 785/CDP7851 in PMO," said Prof. Dr. med. Iris Loew-Friedrich, chief medical officer of UCB and executive vice-president Global Projects and Development. "We will now begin the in depth analysis of the data to prepare for the phase 3 program. The results fuel our energy working towards providing a new treatment option for the millions of women living with PMO."

The 12-month phase 2 study is a multi-centre, international, randomized, placebo-controlled, parallel-group study designed to evaluate the effect of AMG 785/CDP7851 compared to placebo in women with low BMD, and to characterize the safety and tolerability of AMG 785/CDP7851. Approximately 400 postmenopausal women with low BMD (T-scores between -2.0 and -3.5) are enrolled in the study. Treatment arms included dosing at 70, 140 and 210 mg subcutaneously once a month, and 140 and 210 mg every three months, against matched placebo for all treatment groups.

AMG 785/CDP7851 is a humanized monoclonal antibody that binds to and inhibits sclerostin, a protein secreted by bone cells that inhibits bone formation. By binding to and blocking sclerostin, AMG 785/CDP7851 is designed to allow the body to add more bone to the skeleton. Amgen and UCB have collaborated for the development of AMG 785/CDP7851 for the treatment of bone-related conditions, including PMO and fracture healing.

Amgen discovers, develops, manufactures, and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. 

UCB, Brussels, Belgium is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system.

 

Source: Pharmabiz    Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62521&sid=2

CytRx increases clinical sites to 15 in tamibarotene phase II b trial in 1st line NSCLC to expedite patient recruitment

 

CytRx Corporation a biopharmaceutical company specializing in oncology, has expanded enrolment to 15 clinical sites in its phase II b clinical trial with tamibarotene in combination with chemotherapeutical agents for the treatment of patients with advanced Non-Small-Cell Lung Cancer (NSCLC). The large number of sites is expected to accelerate recruitment, and full enrolment of the approximately 140 patients is now anticipated in 12 months. 

“We have opened enrolment in 15 clinical sites in the US and Mexico for our tamibarotene clinical trial in 1st line NSCLC to expedite recruitment for an indication that could represent a blockbuster opportunity,” said CytRx CEO Steven A Kriegsman. “We expect these additional sites will accelerate enrolment, which means we could have data from this phase 2b clinical trial by the end of 2012. What makes NSCLC so compelling is that it is responsible for more deaths than breast, prostate and ovarian cancers combined.”

Daniel Levitt, MD, PhD, CytRx's chief medical officer, said, “Tamibarotene is 10 times more potent than All Trans Retinoic Acid (ATRA), while simultaneously showing properties that suggest it may lead to fewer adverse effects than ATRA. Recent published clinical data demonstrated that ATRA in combination with chemotherapeutical agents was statistically significant as a treatment for advanced NSCLC, which may open the door for tamibartotene based on its greater potency and lower side effect profile than ATRA.”

In December 2010, CytRx initiated the phase II b clinical trial in patients with advanced NSCLC at a single clinical site. In this randomized clinical trial, patients with advanced NSCLC are treated with paclitaxel plus carboplatin and either tamibarotene or placebo. The primary objective of  this trial is to determine the objective response rate (complete and partial responses) and progression-free survival. Secondarily, the trial will evaluate overall survival, quality-of-life and examine the pharmacokinetics of tamibarotene in this population, among other measures. 

A clinical trial conducted by Arrieta et al. and published in the peer-reviewed Journal of Clinical Oncology (June 17, 2010)compared ATRA added to a regimen of paclitaxel plus cisplatin to a regimen of paclitaxel plus cisplatin alone as a treatment for patients with advanced NSCLC. The group administered ATRA plus the chemotherapeutical agents showed improved response rates of 55.8% versus 25.4%, and increased progression-free survival of 8.9 months versus 6.0 months. Median overall survival was increased from 9.5 months to 23.5 months when ATRA was added to the above chemotherapy regimen, representing a 14-month median extension of life. 

More than 222,000 new cases of lung cancer will occur in the US this year and more than 1.5 million worldwide. Deaths due to lung cancer account for the majority of cancer-related deaths (157,000 in the US, 1.4 million worldwide) and the five-year survival ranges between 8-15%. NSCLC accounts for 85-90% of all lung cancers, with subsets adenocarcinoma representing 35-40%, squamous cell carcinoma accounting for 25-30% and large cell carcinoma accounting for 10-15% of lung cancers. 

Tamibarotene is an orally available, rationally designed, synthetic retinoid compound. CytRx holds the North American and European rights to certain tamibarotene intellectual property for the treatment of NSCLC and APL, and retains an option to expand its licenses for the use of tamibarotene in other fields in oncology. 

CytRx Corporation is a biopharmaceutical research and development oncology company engaged in the development of high-value human therapeutics. It also includes tamibarotene, which it is testing in patients with Non-Small-Cell Lung Cancer and which is in a registration clinical trial as a treatment for Acute Promyelocytic Leukaemia (APL).

 

Source: Pharmabiz     Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62523&sid=2

GW Pharma gets US patent for Sativex in cancer pain

 GW Pharmaceuticals plc announces that the United States Patent and Trademark Office has issued a Notice of Allowance for a patent which protects the use of Sativex as a treatment for cancer pain. 

The patent, entitled “Pharmaceutical Compositions for the Treatment of Pain”, provides an exclusivity period until April 2025. The patent specifically covers a method of treating cancer related pain by administering a combination of the cannabinoids cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC), the two principal cannabinoids in Sativex. In addition to this newly granted patent, Sativex is protected by a number of other patents related to different aspects of the product.

Sativex is currently in phase III clinical development as a treatment for cancer pain. Cancer pain represents the lead indication for Sativex in the United States, where the medicine is partnered with Otsuka Pharmaceutical Co. Ltd.

Dr Geoffrey Guy, GW’s chairman, said, “The grant of this US patent covering Sativex as a treatment for cancer pain is part of a broad platform of intellectual property rights which continue to be developed by GW. GW now has 35 patent families as well as other forms of protection such as plant variety rights and proprietary know-how. We believe that this matrix of intellectual property provides GW with a unique position to benefit from the rich promise within the field of cannabinoid therapeutics.”

Sativex is approved in the UK, Spain, Czech Republic, Canada and New Zealand as a treatment of Multiple Sclerosis spasticity.

Cancer pain represents the initial target indication for Sativex in the United States. The phase III cancer pain programme is being performed in conjunction with GW’s licensing partner for Sativex in the US, Otsuka Pharmaceutical Co. Ltd. The programme, which is fully funded by Otsuka, includes two phase III randomised placebo-controlled multi-centre multinational trials as well as a long term extension study. Each phase III trial will include approximately 370 patients and will evaluate the efficacy and safety of Sativex versus placebo over a 5 week treatment period.

Studies suggest that more than one-third of patients with cancer, and more than three-quarters of those with advanced disease, have chronic pain.  Large surveys indicate that optimal opioid therapy does not yield sufficient relief in a substantial proportion of these patients.

GW researches and develops cannabinoid pharmaceutical products for patients who suffer from a range of serious ailments, in particular multiple sclerosis and cancer pain.

 

Source: Pharmabiz         Weblink: http://www.pharmabiz.com/NewsDetails.aspx?aid=62524&sid=2

Friday, April 22, 2011

Boehringer Ingelheim's lead hepatitis C compound moves into phase III

 Boehringer Ingelheim announced the study outline for the pivotal Phase III clinical trials designed to evaluate BI 201335, its investigational once-daily oral protease inhibitor, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV), the most challenging genotype to treat.

In parallel, the U.S. Food and Drug Administration (FDA) has granted Fast Track designations for BI 201335 plus standard-of care (SOC), and as part of the interferon-free combination with the polymerase inhibitor, BI 207127, in chronic genotype-1 HCV patients.

"We are delighted to receive the FDA’s Fast Track designation for both, our BI 201335 plus SOC, and interferon-free combination treatment approaches. If successful, the combination therapy carries the potential for patients to live without the burden of interferon’s side effects," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. "We are committed to bringing BI 201335 forward, with the ambition of improving cure rates for the benefit of those living with hepatitis C."

BI 201335 Phase III Trials*
BI 201335 will be evaluated in multiple randomised, double-blind, placebo-controlled trials in combination with pegylated-interferon and ribavirin (PegIFN/RBV), the current HCV SOC. The Phase III trials include two studies in treatment- naïve and one study in treatment-experienced chronic genotype-1 HCV patients. The two studies in treatment-naïve patients will be conducted in the European Union and Japan, as well as the U.S., Canada, Taiwan and Korea. The study in treatment-experienced patients will be conducted globally. BI 201335 will be dosed once-daily at either 120mg or 240mg in combination with PegIFN/RBV and treatment durations will range from 24 to 48 weeks. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure. These studies are part of a broader Phase III trial programme expected to commence in the second quarter of 2011.

PegIFN-Free Phase II Trials of BI 201335 + BI 207127
In parallel, Boehringer Ingelheim is developing BI 207127, an oral HCV polymerase inhibitor that has completed Phase I clinical trials in combination with BI 201335. Phase II trials evaluating BI 207127 plus BI 201335 in PegIFN-free regimens, both with and without ribavirin, are currently underway. The FDA has designated this investigation as a Fast Track development programme. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.

About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.

About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research programme for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.

Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.

Source: WORLD PHARMA NEWS            Website link: http://www.worldpharmanews.com/boehringer-ingelheim/1633-boehringer-ingelheims-lead-hepatitis-c-compound-moves-into-phase-iii

REACT study to evaluate impact of Daxas® (roflumilast) in patients receiving standard COPD treatment

 Nycomed announced plans for an international phase III/IV study investigating the effect of Daxas® versus placebo on exacerbation rates in COPD patients who are concomitantly treated with fixed combination long-acting-ß2-agonists (LABA) and inhaled corticosteroids (ICS), with or without a long-acting muscarinic antagonist (LAMA). Use of Daxas® with the individual components of fixed combination and triple therapy has already been shown to reduce exacerbations and improve lung function.(1,2) The REACT study is the first to investigate Daxas when used in patients concomitantly treated with fixed combination treatment or triple therapy.

The REACT trial is a 52-week, randomised, double-blind, multi-centre study which will recruit approximately 2,000 patients from 21 countries. The primary endpoint is the reduction of moderate or severe COPD exacerbations per patient per year. Moderate exacerbations are defined as those requiring oral or parenteral glucocorticosteroids and severe exacerbations are defined as requiring hospitalisation and/or leading to death. Other exacerbation endpoints will also be assessed, including the proportion of patients experiencing an exacerbation and time to first, second and third exacerbation. Quality of life will be measured using the COPD Assessment Test (CAT questionnaire).(3)

The trial will recruit patients with severe COPD associated with chronic bronchitis and frequent exacerbations, reflecting the licence indication for Daxas. First patient enrolment is anticipated in second quarter 2011.

Anders Ullman, Executive Vice President, Research and Development at Nycomed, commented: "Many people with COPD, even those with optimum management, continue to have symptoms and frequent exacerbations affecting long-term outcomes and quality of life. We are confident that the REACT trial will provide further insights into how Daxas can be used most effectively and therefore help COPD patients receive the treatment they need."

Peter Calverley, Professor of Respiratory Medicine, University of Liverpool, UK, and Co-ordinating Investigator for the REACT trial, said: "As COPD progresses, patients suffer exacerbations or lung attacks which often require substantial medical intervention and can lead to hospitalisation. Studies have already shown that roflumilast significantly reduces exacerbations and the REACT trial will further our understanding of the role of roflumilast in everyday practice. We know that the outcome of this study will be eagerly awaited by patients and doctors alike."

Daxas was approved in Europe in July 2010 and in the US in February 2011 (US trade name: Daliresp(TM)).

About the REACT trial
The REACT trial is a large, international phase III/IV study that will evaluate the effect of Daxas® (roflumilast) on exacerbation rates in patients with COPD who are treated with fixed combinations of LABA and ICS, with or without LAMA treatment. The study is a 52-week, randomised, double-blind trial which evaluates roflumilast 500 mcg versus placebo on top of combination and triple therapy. The study will recruit approximately 2,000 patients and will be conducted in over 200 centres across 21 countries: Australia, Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Netherlands, Poland, Russia, Slovakia, South Africa, Spain, Turkey, and UK.

About Daxas® (roflumilast)
Daxas (roflumilast) is an orally administered selective phosphodiesterase 4 (PDE4) enzyme inhibitor, which has been shown to inhibit COPD related inflammation with a novel mode of action.(4) Daxas, a once-a-day tablet, is the first drug in a new class of treatment for severe COPD and the first oral anti-inflammatory treatment specifically developed for COPD patients.

Four large randomized placebo controlled trials have shown that roflumilast significantly reduces exacerbations and improves lung function when added to first-line maintenance therapy.

Daxas is generally well tolerated. In clinical COPD trials involving 12,000 patients, the most commonly reported adverse reactions were diarrhoea (5.9%), weight decreased (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1.7%). The majority of these adverse reactions were mild or moderate. These adverse reactions mainly occurred within the first weeks of therapy and mostly resolved on continued treatment.

Other pharmacological treatment for COPD patients includes the use of inhaled bronchodilators and inhaled corticosteroids.

About COPD
COPD remains a significant area of unmet medical need. It is a progressive and irreversible lung disease resulting in difficulty in breathing. The disease is characterised by severe episodes of worsening, called exacerbations or lung attacks. According to World Health Organization (WHO) estimates, 80 million people have moderate to severe COPD worldwide. More than 3 million people died of COPD in 2005, which corresponds to 5% of all deaths globally. The WHO predicts that total deaths from COPD could increase by more than 30% in the next 10 years unless urgent action is taken to reduce the underlying risk factors, especially smoking.

About Nycomed
Nycomed is a privately owned global pharmaceutical company with a diversified portfolio focused on branded medicines in gastroenterology, respiratory and inflammatory diseases, pain, osteoporosis and tissue management. A range of OTC products completes the portfolio.

Its R&D is structured around collaborations. In-licensing and expanding in emerging markets are cornerstones of the company's growth strategy.

Nycomed employs 12,500 associates worldwide, and its products are sold in more than 100 countries. It has strong platforms in Europe and in fast-growing markets such as Russia/CIS, Latin America, Asia and the Middle East. In the US and Japan its products are available through best in class partners.

Headquartered in Zurich, Switzerland, the company generated total sales of € 3.2 billion in 2010 and an adjusted EBITDA of € 851 million.

1. Fabbri LM, Calverley PMA, Izquierdo-Alonso JL et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: two randomised clinical trials; The Lancet 2009; 374: 695-703
2. Rennard S, Calverley PMA, Goehring UM et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast - the importance of defining different subsets of patients with COPD; Respiratory Research 2011; 12:18
3. Jones PW, Harding G, Berry P, et al. Development and first validation of the COPD Assessment Test; Eur Respir J 2009; 34(3): 648-654
4. Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast - a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease; Pulmonary Pharmacology & Therapeutics 2010: 23(4): 235-56

 

Source: WORLD PHARMA NEWS      Website link: http://www.worldpharmanews.com/nycomed/1630-react-study-to-evaluate-impact-of-daxasr-roflumilast-in-patients-receiving-standard-copd-treatment

Pfizer to Sell Capsugel to KKR

 Pfizer and Kohlberg Kravis Roberts & Co L.P. (together with its affiliates, "KKR") have entered into an agreement whereby an affiliate of KKR will acquire Pfizer's Capsugel business for $2.375 billion in cash. Capsugel, the world leader in hard capsules and an innovator in drug-delivery systems, generated approximately $750 million in revenue and manufactured more than 180 billion hard capsules in 2010.

"The transaction is an endorsement of Capsugel’s consistent success to date and its potential for future growth with KKR, a firm with deep industry expertise and a long history of partnering with market-leading businesses to take them to the next level," said Guido Driesen, President and General Manager of Capsugel. "Capsugel's employees and I are excited to work with KKR and eager to enhance the value of our business in partnership with our customers."

Over the past 34 years, KKR has invested in more than 185 transactions with a total value of more than $435 billion. KKR’s current private equity portfolio includes over 60 portfolio companies with over $210 billion of annual revenues and more than 900,000 employees.

Henry R. Kravis and George R. Roberts, Co-Founders, Co-Chairmen and Co-CEOs of KKR, stated, "Capsugel has an excellent portfolio and outstanding reputation for providing high-quality, innovative drug-delivery solutions. We look forward to working with Capsugel's talented employees and investing in this business. We share Capsugel's enthusiasm for its future potential to grow, develop and continue to deliver an unmatched quality of products."

Pfizer expects to make additional repurchases of its common stock on the open market during 2011 as a result of this transaction, assuming completion this year. Pfizer's repurchases of its common stock funded by Capsugel sale proceeds would be in addition to the previously announced anticipated repurchase of approximately $5 billion of shares planned for 2011. Pfizer will also continue to look to identify and invest in other opportunities to maximize its value, including business development.

As a result of this transaction, Pfizer is updating its previous 2011 Reported Revenue guidance range from $66.0 - $68.0 billion to $65.2 - $67.2 billion, and its previous 2012 Reported Revenue target range from $63.0 – $65.5 billion to $62.2 - $64.7 billion, while maintaining all other elements of its 2011 financial guidance and 2012 financial targets.

Capsugel will maintain a corporate presence in the United States, with its global headquarters located in New Jersey. All Pfizer colleagues currently dedicated to this business will be transferred to Capsugel, which will be under the leadership of Guido Driesen upon the completion of the transaction.

The transaction is subject to customary closing conditions, including regulatory approval in certain jurisdictions, such as the U.S. and the European Union, among others. The companies expect to complete the transaction in the third quarter of 2011, assuming the receipt of the required regulatory clearances and satisfaction of other closing conditions.

Pfizer's financial advisors for the transaction were Morgan Stanley & Co. Incorporated and Guggenheim Securities, LLC. Cadwalader, Wickersham & Taft LLP and White & Case LLP acted as legal counsel for Pfizer. Simpson Thacher & Bartlett LLP acted as legal counsel for KKR.

About Capsugel
Capsugel is the world's leading provider of hard capsules and an innovator in drug delivery systems for the pharmaceutical, OTC and health and nutrition industries. Capsugel offers a comprehensive array of products and services, from hard gelatin, vegetarian and liquid-filled capsules, to innovative R&D equipment and liquid formulations as part of its Licaps® Drug Delivery System.

About KKR
Founded in 1976 and led by Henry Kravis and George Roberts, KKR is a leading global investment firm with $61.0 billion in assets under management as of December 31, 2010. With 14 offices around the world, KKR manages assets through a variety of investment funds and accounts covering multiple asset classes. KKR seeks to create value by bringing operational expertise to its portfolio companies and through active oversight and monitoring of its investments. KKR complements its investment expertise and strengthens interactions with investors through its client relationships and capital markets platforms. KKR is publicly traded on the New York Stock Exchange (NYSE: KKR).

About Pfizer
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small- molecule medicines and vaccines, as well as nutritional products and many of the world's best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world's leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

 

Source: WORLD PHARMA NEWS                  Webite link: http://www.worldpharmanews.com/pfizer/1634-pfizer-to-sell-capsugel-to-kkr

Novartis completes acquisition of majority stake in Zhejiang Tianyuan expanding vaccines presence in China

 Novartis completed the transaction to acquire an 85 percent stake in the Chinese vaccines company Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. This acquisition provides Novartis with an expanded presence in the Chinese vaccines market and is expected to facilitate the introduction of additional Novartis vaccines into China where there continues to be tens of thousands of new cases of vaccine-preventable diseases each year[1].

"This agreement combines the strength of our vaccines R&D strategy and pipeline with Tianyuan's deep knowledge of the vaccines market in China, enabling us to better deliver a broad range of vaccines to the Chinese people," said Andrin Oswald, Head of Novartis Vaccines and Diagnostics. "Our collaboration with Tianyuan marks an important step in our strategy and long-standing commitment to improve healthcare in China by delivering effective vaccines that prevent diseases."

Novartis aspires to become a vaccine industry leader in China through targeted investments in vaccines innovation and manufacturing technologies. Novartis plans to collaborate with Tianyuan to strengthen its vaccines portfolio and pipeline, as well as align production processes and quality standards. As part of its commitment to improving healthcare for the Chinese people, Novartis also plans to explore new vaccine developments to address unmet medical needs in China.

"We look forward to working with Novartis to build a broader portfolio of novel and high-quality vaccines to help prevent disease in China and globally," said Mr. Ding Xiaohang, who is the founder, Chairman and CEO of Tianyuan and will continue his position while holding a minority stake. "We have already identified several joint development programs that could be implemented in China over the next ten years, with the potential of launching key products responding to unmet medical needs in the mid-term."

China is the world's third largest vaccines market, with annual industry sales of more than USD 1 billion and expectations for sustained double-digit growth in the future, given the government's commitment to improve access to quality healthcare.

About Novartis
Novartis Vaccines and Diagnostics is a division of Novartis, focused on the development of preventive treatments. The division has two businesses: Novartis Vaccines and Novartis Diagnostics. Novartis Vaccines is the world's fifth-largest vaccines manufacturer and second-largest supplier of flu vaccines in the US. The division's products also include meningococcal, pediatric and travel vaccines. Novartis Diagnostics, the blood testing business, is dedicated to preventing the spread of infectious diseases through the development of novel blood-screening tools that protect the world's blood supply.

Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates (including 16,700 Alcon associates) and operate in more than 140 countries around the world.

About Tianyuan
Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., which was founded as a private enterprise by Mr. Ding Xiaohang, entered the Chinese vaccines industry in 1994 with the first vaccine in China against Hemorrhagic Fever with Renal Syndrome (HFRS) caused by hantaviruses. Tianyuan has since become one of the country's leading private manufacturers and distributors of vaccines with approximately 400 associates and an R&D/manufacturing site in Hangzhou (near Shanghai).

 

Source: WORLD PHARMA NEWS       Website link: http://www.worldpharmanews.com/novartis/1624-novartis-completes-acquisition-of-majority-stake-in-zhejiang-tianyuan-expanding-vaccines-presence-in-china

Amgen's First Quarter 2011 Revenue Increased 3 Percent to $3.7 Billion

 Amgen (NASDAQ: AMGN) reported adjusted earnings per share (EPS) of $1.34 for the first quarter of 2011, an increase of 3 percent compared to $1.30 for the first quarter of 2010. Adjusted net income decreased 2 percent to $1,258 million in the first quarter of 2011 compared to $1,282 million in the first quarter of 2010.

Total revenue increased 3 percent during the first quarter of 2011 to $3,706 million versus $3,592 million in the first quarter of 2010.

"We had solid revenue growth in the first quarter," said Kevin Sharer, chairman & CEO. "Prolia continues to build momentum and XGEVA is off to a strong start. Our operating costs grew in the quarter as we absorbed the new U.S. Healthcare Reform Excise Fee, invested in launches of Prolia and XGEVA and in clinical development programs transitioning to Phase 3."

Adjusted EPS and adjusted net income for the first quarter of 2011 and 2010 exclude, for the applicable periods: stock option expense; certain expenses related to acquisitions and actions to improve cost efficiencies; non-cash interest expense resulting from a change in accounting for our convertible notes; and certain other items. These adjustments and other items are presented on the attached reconciliations.

On a reported basis and calculated in accordance with United States (U.S.) Generally Accepted Accounting Principles (GAAP), Amgen's GAAP diluted EPS were $1.20 in the first quarter of 2011, an increase of 2 percent compared to $1.18 in the same quarter last year. GAAP net income of $1,125 million in the first quarter of 2011 decreased 4 percent from $1,167 million in the first quarter of 2010.

Amgen's first quarter of 2011 financial results were positively impacted by the recently enacted Puerto Rico excise tax associated with the Company's manufacturing operations in Puerto Rico. This excise tax is accounted for as a manufacturing cost that is capitalized in inventory and expensed when the products are sold. For U.S. income tax purposes, a significant portion of the excise tax results in a foreign tax credit that is recognized when the tax is paid. This difference in the timing of recognizing the expense and the applicable tax credit positively impacted the first quarter of 2011 financial results.

About Amgen
Amgen discovers, develops, manufactures, and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives.

Source: WORLD PHARMA NEWS          Website link:http://www.worldpharmanews.com/amgen/1654-amgens-first-quarter-2011-revenue-increased-3-percent-to-37-billion

Thursday, April 21, 2011

Bangalore India Bio 2011’ focuses on biotech for improving quality of life, starts on May 4

 Karnataka’s Department of Information Technology, Bio-Technology and Science & Technology, Vision Group on Biotechnology and MM Activ Sci-Tech Communications have announced that the 11th edition of the annual  ‘Bangalore India Bio 2011’ will be held from May 4 to May 6, 2011 at the Bangalore International Exhibition Centre (BIEC) on Tumkur Road, Bangalore. The theme of the event is ‘biotech for improving the quality of life’ in the areas of biopharmaceuticals, clinical research, biomedical technology, bio business, bio collaborations and industrial biotechnology.

Last year, the Karnataka government rechristened the Bangalore Bio event as Bangalore India Bio 2010. The name change comes going by the rapid growth of the sector in the last decade not only on a national level but from a global perspective.

The  three-day event is recognized as one of the largest biotech events in Asia and has a positive impact on the industry. According to the organizers, the three day event with 21 sessions and 102 speakers has already attracted 8 companies from Belgium, 30 from Europe, 12 from France and 8 from USA.

“The event has positioned India as one of the top destinations for biotech R&D, bio-services and market for end-products. The global biotech industry's response over the years is a proof of its popularity. India is an important destination for the biotech industry worldwide. Bangalore India Bio plays a major role in business development for India in the global biotech arena and has entrenched itself as a hub for innovations & collaborations,” stated the organizers. 

“This year’s show would be a platform for the international biotech companies to connect with leaders in India’s Life Sciences Industry, besides policy makers and regulators and biotech states.” he added.

The 11th edition will have an International Exhibition, Multi-Track Conference, BioPartnering India, CEO Conclave, Bio-IP Zone, Poster Session, BioQuiz and the Bio- Excellence Awards Function. Over 170 exhibitors, 1000 delegates and over 5000 business visitors from across the world and India are expected to participate in the event. Countries expected to participate are USA, Canada, UK, France, Chile, Cuba, Mexico, Germany, Spain, Australia, New Zealand, South Africa, Japan, Singapore, Malaysia, China, Korea & UAE.

The CEO Conclave is an exclusive gathering of CEOs, R&D Heads, Policy-makers, Venture Capitalists and Investment Bankers. After the success of the Bio-IP Zone initiative last year, this year it will enable leading IP firms to come to address issues like licensing, valuation, patents, trademarks & copyright. Bio Excellence Awards, Exhibitor Awards and Poster Awards will be presented during the programme. Poster Session – ‘Walkway of Discovery’ will provide an opportunity to present innovative ideas, which have the potential to make a significant impact in the field of biotechnology. A  state-level  BioQuiz, introduced last year attracted 128 students from 64 colleges across Karnataka and this year more participants are expected, stated the organizers.

Last year’s event had 366 delegates, 219 companies from 25 countries. Over 800 meetings were facilitated for not only start-ups but established pharma and biotech companies.

Source: Pharmabiz             Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62479&sid=1

Bangalore India Bio 2011’ focuses on biotech for improving quality of life, starts on May 4

 Karnataka’s Department of Information Technology, Bio-Technology and Science & Technology, Vision Group on Biotechnology and MM Activ Sci-Tech Communications have announced that the 11th edition of the annual  ‘Bangalore India Bio 2011’ will be held from May 4 to May 6, 2011 at the Bangalore International Exhibition Centre (BIEC) on Tumkur Road, Bangalore. The theme of the event is ‘biotech for improving the quality of life’ in the areas of biopharmaceuticals, clinical research, biomedical technology, bio business, bio collaborations and industrial biotechnology.

Last year, the Karnataka government rechristened the Bangalore Bio event as Bangalore India Bio 2010. The name change comes going by the rapid growth of the sector in the last decade not only on a national level but from a global perspective.

The  three-day event is recognized as one of the largest biotech events in Asia and has a positive impact on the industry. According to the organizers, the three day event with 21 sessions and 102 speakers has already attracted 8 companies from Belgium, 30 from Europe, 12 from France and 8 from USA.

“The event has positioned India as one of the top destinations for biotech R&D, bio-services and market for end-products. The global biotech industry's response over the years is a proof of its popularity. India is an important destination for the biotech industry worldwide. Bangalore India Bio plays a major role in business development for India in the global biotech arena and has entrenched itself as a hub for innovations & collaborations,” stated the organizers. 

“This year’s show would be a platform for the international biotech companies to connect with leaders in India’s Life Sciences Industry, besides policy makers and regulators and biotech states.” he added.

The 11th edition will have an International Exhibition, Multi-Track Conference, BioPartnering India, CEO Conclave, Bio-IP Zone, Poster Session, BioQuiz and the Bio- Excellence Awards Function. Over 170 exhibitors, 1000 delegates and over 5000 business visitors from across the world and India are expected to participate in the event. Countries expected to participate are USA, Canada, UK, France, Chile, Cuba, Mexico, Germany, Spain, Australia, New Zealand, South Africa, Japan, Singapore, Malaysia, China, Korea & UAE.

The CEO Conclave is an exclusive gathering of CEOs, R&D Heads, Policy-makers, Venture Capitalists and Investment Bankers. After the success of the Bio-IP Zone initiative last year, this year it will enable leading IP firms to come to address issues like licensing, valuation, patents, trademarks & copyright. Bio Excellence Awards, Exhibitor Awards and Poster Awards will be presented during the programme. Poster Session – ‘Walkway of Discovery’ will provide an opportunity to present innovative ideas, which have the potential to make a significant impact in the field of biotechnology. A  state-level  BioQuiz, introduced last year attracted 128 students from 64 colleges across Karnataka and this year more participants are expected, stated the organizers.

Last year’s event had 366 delegates, 219 companies from 25 countries. Over 800 meetings were facilitated for not only start-ups but established pharma and biotech companies.

Source: Pharmabiz             Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62479&sid=1

Mylan launches generic version of Famvir tablets

 Mylan Inc. announced that its subsidiary Mylan Pharmaceuticals Inc. has launched famciclovir tablets, 125 mg, 250 mg and 500 mg, the generic version of Novartis' Famvir tablets, a treatment for herpes.  

Famciclovir tablets had US sales of approximately $196 million for the 12 months ending December 31, 2010, according to IMS Health.

Currently, Mylan has 165 ANDAs pending US FDA approval representing $98.5 billion in annual sales, according to IMS Health. Forty-six of these pending ANDAs are potential first-to-file opportunities, representing $25.9 billion in annual brand sales, for the 12 months ending June 30, 2010, according to IMS Health.

Mylan Inc.ranks among the leading generic and specialty pharmaceutical companies in the world and provides products to customers in more than 150 countries and territories. The company maintains one of the industry's broadest and highest quality product portfolios supported by a robust product pipeline; operates one of the world's largest active pharmaceutical ingredient manufacturers; and runs a specialty business focused on respiratory, allergy and psychiatric therapies. 

Source: Pharmabiz           Website Link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62507&sid=2

Phase III data shows NVA237 significantly improves lung function with good safety profile in COPD patients

 Sosei Group Corporation (Sosei) announces that NVA237, a long-acting muscarinic antagonist (LAMA) being investigated as a once daily treatment for chronic obstructive pulmonary disease (COPD), achieved its primary end point in a phase III study.

As part of its first quarter earnings release, Novartis confirmed results from the first phase III clinical trial with once-daily NVA237 (glycopyrronium bromide) show that it significantly improved lung function while demonstrating a good safety profile in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

The pivotal double-blind 26-week GLOW1 study met its primary endpoint by demonstrating superior bronchodilation to placebo at 12 weeks measured by trough FEV1 (i.e. forced expiratory volume in one second), a standard measure of lung function (p<0.001).

The incidence of adverse events was similar in the NVA237 treated patients and in those receiving placebo. Detailed data will be presented at a scientific congress in H2 2011.

Shinichi Tamura, CEO of Sosei, said: "We are very encouraged that results from the initial pivotal GLOW1 trial, showing significantly increased lung function with a positive safety profile, have provided further confirmation of the clinical potential of NVA237 as a novel once-daily LAMA therapy for COPD patients.”

NVA237 was licensed to Novartis in April 2005 by Sosei and its co-development partner Vectura. Novartis intends to launch NVA237 in 2012 as a once-daily monotherapy for COPD. The first launch for QVA149; the combination of NVA237 with Novartis’ once-daily, long-acting beta2-agonist (LABA), indacaterol, is planned for 2013. Indacaterol is now approved in more than 50 countries and available in more than 20, with US approval dependent on an FDA decision expected in July 2011.

COPD is a chronic obstruction of the airways which affects 210 million people worldwide1 and is projected to be the third leading cause of death by 20202. It is a progressive lung disease with symptoms including chronic bronchitis and/or emphysema, which slowly progresses and eventually leads to a largely irreversible loss of lung function. While there is no cure, bronchodilators such as LAMAs and LABAs make breathing easier by enlarging the patient’s airways, and are recognised in international guidelines as an integral part of the treatment for COPD.

Sosei is an international biopharmaceutical company anchored in Japan with a global reach. It practises a reduced risk business model by acquiring compounds from, and bringing compounds into, Japan through exploitation of its unique position within global markets.

Source: Pharmabiz                   Website Link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62509&sid=2

Amira Pharma's lead LPA1 antagonist AM152 to treat idiopathic pulmonary fibrosis gets US FDA orphan drug status

Amira Pharmaceuticals, Inc. announced that AM152, the company’s lead LPA1 antagonist, has been granted an orphan drug designation by the US Food and Drug Administration for the treatment of Idiopathic Pulmonary Fibrosis. Commonly referred to as IPF, this fibrotic disease affects the lungs of patients and their ability to breathe.

“This is an important development for Amira, and potentially patients suffering from IPF, as we continue to move this promising therapeutic candidate forward in development,” said Bob Baltera, chief executive officer. “We are currently completing our phase I studies with AM152 and expect to begin a phase II study by the end of 2011 or in early 2012. Currently there are no FDA-approved therapies for IPF, and we look forward to better understanding the potential therapeutic benefit of an LPA1 antagonist in this disease area.”

AM152 is a Lysophosphatidic Acid (LPA) receptor 1 antagonist. Activation of the LPA1 receptor by LPA has been implicated in a number of disease processes, including tissue fibrosis. LPA1 receptor antagonists have displayed efficacy in a wide range of preclinical fibrosis models, including lung, skin, eye, liver and kidney.

The United States Orphan Drug Act of 1983 was created to promote and support the development of new drug therapies for diseases that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides a sponsor seven years of market exclusivity for the designated therapeutic indication in the United States, from the point at which the therapy is granted marketing approval. It also provides access to regulatory support from the FDA, potential FDA fee reductions and tax credits related to development expenses.

Amira Pharmaceuticals is a small molecule pharmaceutical company focused on the discovery and early development of new drugs to treat inflammatory and fibrotic diseases.

 

Source: Pharmabiz                Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62510&sid=2

NIH scientists identify gene that could hold the key to muscle repair

 

Researchers have long questioned why patients with Duchenne Muscular Dystrophy (DMD) tend to manage well through childhood and adolescence, yet succumb to their disease in early adulthood, or why elderly people who lose muscle strength following bed rest find it difficult or impossible to regain. Now, researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, are beginning to find answers in a specialized population of cells called satellite cells. Their findings, reported in the journal Genes & Development, suggest a potential therapeutic target for conditions where muscle deterioration threatens life or quality of life.

Key to the development of skeletal muscle of the embryo and foetus, satellite cells continue to actively increase muscle mass through infancy. After that, they decrease in number and become quiescent, or inactive, until they are activated by injury or degeneration to proliferate. The process, which enables the body to repair damaged muscle, works quite well — to a point, says Vittorio Sartorelli, MD, senior investigator in the NIAMS Laboratory of Muscle Stem Cells and Gene Regulation and lead author of the study.

For example, when a young person experiences muscle loss after a period of inactivity, muscle rebuilds as soon as activity is resumed. However, in the elderly, muscles lose that capacity. Similarly, in patients with DMD, the initial phases of muscle degeneration are effectively counteracted by the ability of satellite cells to regenerate.

“That is why people can survive until they are 20 years old without much of a problem, but, at a certain point, satellite cells stop proliferating,” said Dr Sartorelli. “That is the point at which the patient will start developing weakness and problems that will ultimately lead to death.”

Suspecting a genetic switch that might turn off satellite cell proliferation in these circumstances, the scientists looked to a gene called Ezh2, known to keep the activity of other genes in check. When they genetically inactivated Ezh2 in satellite cells of laboratory mice, the mice failed to repair muscle damage caused by traumatic injury — satellite cells could not proliferate.

Ezh2 expression is known to decline during aging, and the new research in mice suggests that therapies to activate Ezh2 and promote satellite cell proliferation might eventually play a role in treating degenerative muscle diseases.

“We will not be able to cure the muscular dystrophies with this approach because the mutation in the gene that causes the diseases would remain. But certainly, if we can extend the period in which the satellite cells proliferate and compensate for the underlying defect, we might increase the lifespan of people with muscular dystrophy. We could certainly increase their quality of life,” said Dr Sartorelli.

Likewise, in the elderly, tweaking the gene in satellite cells would not increase their lifespan, but could increase their quality of life by helping to prevent falls and enabling them to move and walk better and go about their daily activities.

Dr Sartorelli cautions that while the identification of Ezh2's role is a crucial step, any therapies are still many years away.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the US Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. 

NIH, the nation's medical research agency, includes 27 Institutes and Centres and is a component of the US Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.


Source: Pharmabiz         Website Link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62511&sid=2

 

Malvern’s Zetasizer Nano proves to be the perfect instrument for a student environment

 While viruses are so often seen as the enemy, modern scientific techniques may soon be able to harness the strengths of a virus for drug delivery systems that are designed to treat diseases, rather than cause them. Using a Zetasizer Nano particle characterisation system from Malvern Instruments, researchers at Indiana University’s (IU) molecular and cellular biochemistry department have been studying self-assembled virus-based drug delivery systems that can be tuned to a particular size enabling the uptake of specific functional cargo.

Dr Stella Aniagyei, post doctoral research associate at the IU’s molecular and cellular biochemistry department explains, “Viruses tend to be nanosised, symmetrical and structurally consistent with a narrow size distribution. Despite this apparent biological simplicity, viruses are extremely good at delivering their own genome to living biological tissue. This makes them a prime target for biological engineers looking for an efficient transportation device that will deliver drug directly to infected cells.”

“Here at IU’s Nanocharacterization facility, the Malvern Zetasizer Nano is the ‘go to’ instrument for characterisation of assembled product,” said Dr Aniagyei. “Structures closely resembling virus give a narrow size distribution. If they don’t, then we know the process has gone off the biological path. We are currently looking at aggregation limits to move towards defining optimum ionic conditions for the assembly of nucleic acid binding to Gag proteins [one of the nine genes in the retrovirus RNA genome.”

Malvern’s Zetasizer range uses light scattering techniques to measure hydrodynamic size, zeta potential and molecular weight of proteins and nanoparticles. According to Dr Aniagyei, “Malvern’s Zetasizer Nano is very useful for protein characterisation. The ease with which it can be used makes it the perfect instrument for the student environment. It definitely is one of the easiest instruments I’ve had to work with.”

IU is already in the spotlight having just received $900,000 from the ovarian cancer research fund, or OCRF, to help them prepare the new drug SGI-110 for clinical trials in patients whose once-thwarted ovarian cancer has returned. However, this work is not the only IU project at the cutting edge. Established on July 1 2009, the Department of Molecular and Cellular Biochemistry was the first science department created on the Indiana University Bloomington campus in 33 years. Linking biology, chemistry, and medical sciences, the department’s main focus is on the priority areas of structural virology and virus assembly.

Source: Express Pharma          Website Link: 

http://www.expresspharmaonline.com/20110430/pharmaally04.shtml

 

 

Importance of UID (Unique Identification Code) for pharma products

 The problem of counterfeit product is being faced by all the major brands in every kind of segment like pharmaceuticals, electronics / FMCG's / edibles / auto parts etc. The situation is so grave that the controlling of this problem has become major task of the manufacturers. Manufacturers are not only loosing sales and profits but also loosing the ultimate consumer's loyalty to its brand, which is the most serious issue and adversely affecting the company's market share in long term. The counterfeits are so similar to the original that it becomes difficult task for the consumer to differentiate between them. We have to do something either on the product or on the packaging, which makes the brand different from its counterfeits.

Lasersec (India) are providing solutions, which can provide utmost security to the brands. Its major objective is to help the end customers of various brands to distinguish the original from the counterfeits. With a mission to fight against counterfeits, it started its operation in the year 1998 and worked with many major domestic as well as off shore brands with high repute. Lasersec's strong R&D division came up with up to date solutions as per changes in global business environment from time to time. 2004 was a landmark year for Lasersec, in which it's product was rewarded with the World Star Award from the World Packaging Organization for its fusion of blister and holographic effect. At present it has facility to provide holographic solutions on almost all possible surfaces. With a new printing unit it provides all in house Labeling solutions with holographic effect to make it very effective for its clients in terms of cost and time.

Lasersec with UID (Unique Identification Code):

As the technology was advancing every minute, all conventional anti spurious solutions were losing its effectiveness. Industry required solution for their brands to position them out of the reach of the counterfeiters. To come up to the need of the hour Lasersec has equipped itself with UID to provide a full proof anti spurious solution to its users. The end customer needs some assistance at the place of purchase from the company's side to be able to differentiate the original from the duplicate very conveniently. UID does exactly the same thing.

UID is a particular software generated alpha-numeric random code which is given to each unit of product. This software is designed by us in such a way that it will never produce the same nos. It has been the result of various permutation and combinations. At the time of purchase, the customer needs to send an SMS with that UID to a particular long code at nominal SMS tariff to ensure the genuinity of the product. The customer gets a default informatory response from the company's side to ensure authenticity and with awareness or instructions of usage of the product. The total process takes five to ten seconds.

The number of attempts to validate a particular product, It can be pre-controlled as well as regulated to ensure no reuse of the code by the duplicators. If it sends a normal default response for the first attempt, for the second attempt it will send a different response informing its earlier validation. The default responses are of course as set by the product manufacturers and can be up-dated or changed from time to time. A fully automated process eliminates all chances of errors.

There are few other major benefits of UID. UID provides a regular and a very useful database to the manufacturer with mobile number, location, frequency of purchase and mobile numbers with location, attempting validation with wrong code. This will again help the manufacturer locate the most effected locations of the market by the duplicates, so one can take required necessary steps particularly there.

With all the above mentioned features and benefits, UID become a full proof tool to fight the counterfeits in the market and eliminate them from the root. The manufacturers must use it to retain its satisfied customers in the long run. The pharma industry is surely one which can reap the maximum benefit out of it as people wants double assurance of the medicines genuinity. Edible, auto ancillaries are other major segments where the spurious products are playing a havoc in the market. The various Governments in Africa and Europe have already made it mandatory for pharma products. Country like India with such a huge and unorganised retail market will surely see the same in near future.

Source: Express Pharma        Website Link: http://www.expresspharmaonline.com/20110430/packagingspecial05.shtml

FDCA introduces online pharmacy registration

 The Gujarat Food Drug Control Administration (FDCA) recently expanded the ambit of its e-governance service in the Gujarat state, with the launch of the online registration process of self-licensing for pharmacy retail and whole-sale dealers. . This has been implemented in March and now is in full swing.

Hemant Koshia, Commissioner, Food & Drugs Control Administration (FDCA) disclosed his team's approach saying, ”We have developed this new software internally with the help of National Informatic Centre (NIC) of Gujarat. In mid-March we introduced online registration software in the state of Gujarat, and definitely this will smoothen the registration process for pharmacy stores. It took us nearly a year's time to finish this task and on a continuous basis we will be upgrading it further. ”

At present, there are 26,762 pharmacy stores in Gujarat and FDCA receives approximately 150 new registration applications per month. With the help of this new technology, applicants can apply online and can check the status online as well. Koshia elaborates on the advancement of the technology and its benefits to the masses as it is an electronic system, it would be dispense with the delay for both wholesale dealers and retailers, thereby ensuring efficiency. The application will require details like owner/ partners name, pharmacy and pharmacist details, pharmacy's registration number, license number, issue date with validity date by the FDA inspectors, details of the different samples collected by the inspectors with analysis report.

He continues, “We have kept Form 19 online which is useful for the applicant for online registration. Applicant can download it as well as submit his request online. The only thing he needs to do is to mention his authentic mobile number. After receiving data, we will send the requests to respective districts and from there further action will be taken by the authorised district inspectors. This will enhance our capability and work will get done more efficiently. “

 

Source: Express Pharma                  Website Link: http://www.expresspharmaonline.com/20110430/market03.shtml

Uloric is First New Gout Drug in More Than 40 Years

The FDA has approved Uloric, the first new gout drug in more than 40 years, according to Uloric's maker, Takeda Pharmaceuticals. Uloric, taken once daily by mouth, is approved for the chronic management of hyperuricemia (elevated levels of uric acid) in gout patients. Uloric works by blocking an enzyme called xanthine oxidase, which helps prevent uric acid production, lowering elevated uric acid levels, according to Takeda. In 2005, the FDA refused to approve Uloric because there were slightly more deaths and heart problems in patients taking the drug than in patients taking allopurinol, another gout drug. As people with gout problems already are at higher risk of heart disease, the FDA issued an "approvable" letter, noting that Uloric could be approved if this safety question were addressed. Takeda resolved the safety question by performing a large new phase III clinical trial that enrolled more gout patients than the two previous phase III trials combined. The new study found no more deaths and no more heart problems in patients taking Uloric than in patients taking allopurinol.

Sylatron

Generic Name: peginterferon alfa-2b Date of Approval: April 6, 2011 Company: Merck FDA Approves Sylatron The U.S. Food and Drug Administration (FDA) has approved Sylatron (peginterferon alfa-2b) for injection, for subcutaneous use. Sylatron is indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy. Sylatron Medication Guide Read this Medication Guide before you start taking Sylatron, and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment. Important information about Sylatron Sylatron can cause serious mental health problems which can lead to suicide. Signs and symptoms can include: depression (feeling so sad or hopeless that it interferes with your life or you have thoughts of hurting yourself) aggressive behavior towards others, or thoughts of hurting others memory changes and confusion

Wednesday, April 20, 2011

Solid lipid nanoparticles: A drug carrier system

 

 Solid lipid nanoparticles (SLN) are a type of nanoparticles. They are submicron colloidal carriers which are composed of physiological lipids, dispersed in water or in aqueous surfactant solutions. SLN have wide range of advantages over other types of nanoparticles. These include availability of large-scale production methods and no signs of cytotoxicity, which are main hindrances in the application of other types of nanoparticles. Hot and cold homogenization techniques are mainly employed for its production. They are mainly evaluated on the basis of their drug release profile and particle internal structure. The products based on SLN are under development. They have a very wide range of applications in cosmetics and pharmaceuticals. They can be applied for any purpose, for which nanoparticles have a distinct advantage. Thus, SLN can be used extensively as an alternative to the existing drug carrier systems, providing more flexibility with respect to the area of applications and also aspects for commercialization.

 

Introduction   Top


Over the past few years, significant research has been carried out on nanoparticles with their applications in medicine. Nanotechnology can be defined as "the design, production and application of structures, devices and systems by controlled management of size and shape at the nanoscale that produces structures, devices and systems with at least one new property." [1] The nanosize of these particles has a profound influence on their properties and characteristics. This influence is probably because at the nanolevel, there is increase in volume to surface area ratio which eventually attributes to their high reactivity. In addition, quantum effects are more prominent with decrease in size, thereby having effect on the properties of these nanoparticles. Nanotechnology has had a huge impact on the drug delivery- and drug discovery-related areas.

Nanomaterials may be produced in one dimension, two dimensions, or in three dimensions.


   Nanomaterial in One Dimension   Top


Nanomaterial in one dimension may include engineered surfaces and thin films. For example, thin films in silicon-integrated circuit industry. Further advances are being made to control the composition and smoothness of surfaces.


   Nanomaterials in Two Dimensions   Top


These include nanotubes (organic and inorganic) and nanowires.

Carbon nanotubes

These organic nanotubes were first observed by Sumjo lijima in 1991. Carbon nanotubes (CNTs) may be single walled (one tube) or multiwalled (several concentric tubes). CNTs are few nanometers in diameter and several nanometers to centimeters long. Their high conductivity and mechanical strength can be utilized for a variety of purpose. [2],[3] 

Inorganic nanotube

Inorganic nanotubes are based on layered compounds such as molybdenum disulfide, silicon. They have excellent lubricant properties. Additionally, they have very high catalytic reactivity and high capacity for hydrogen and lithium storage. [4] 

Nanowires

Nanowires are semiconductor wires made from a wide range of materials like silicon, gallium nitride, indium phosphide, etc. They have excellent optical, electrical, and magnetic properties. These are prepared by self-assembly techniques.


   Nanomaterials in Three Dimensions   Top


Fullerenes (C60)

Kroto and Richard Smalley discovered a new class of carbon compounds, carbon 60, and named it "buckminsterfullerene." [5] C60 are spherical molecules about 1 nm in diameter. They are applied as miniature ball bearings to lubricate surfaces, drug delivery vehicles, and electronic circuits.

Dendrimers

Dendrimers are spherical polymer molecules formed through self-assembly process. They can be used as drug-delivery carrier. [6] 

Quantum dots

Quantum dots are semiconductor particles made small enough so that quantum effects begin to dominate. There is change in chemical, optical, and electrical properties.

Nanoparticles

Nanoparticles have diameter less than 100 nm. They may be made up of polymers (polymeric nanoparticles), lipids (lipid nanoparticles), or other such materials.

Solid lipid nanoparticles (SLN) are a type of nanoparticles. The present article deals in detail with SLN, including its definition, potential advantages, preparation techniques, and applications in medicine.


   Definition of Solid Lipid Nanoparticles   Top


Definition of Solid Lipid Nanoparticles (SLN) are nanoparticles that are made from solid lipids or lipid blends. It is similar to an oil-in-water emulsion where the liquid lipid (oil) of the emulsion has been replaced by solid lipid in SLN. Lipids used for the synthesis of SLN may include various types of waxes, triglycerides, and complex glycerides. [7] 


   Advantages of SLN as a Drug Carrier System   Top


First of all, SLN are made up of physiologically compatible and tolerable lipids, and hence they are not toxic to the body. Depending upon the incorporation model, the drug release can be controlled as immediate release or sustained release. In addition, they offer protection to the encapsulated drug within them which may be labile and thereby prevent their degradation. They also have advantages of site-specific targeting and of being stable over a period of time. [8] 


   Preparation Techniques   Top


One of the important advantages of SLN is its cost-effective large-scale production. Various different methods for the production of SLN include high-pressure homogenization method, SLN production through microemulsions, double emulsion method, solvent emulsification-evaporation technique, and sonication method. [8] 

Of the above methods, high-pressure homogenization method is commonly used. [9] This method is performed at elevated temperatures or at or below room temperature. The former is called as hot high-pressure homogenization technique, while the latter is called as cold high-pressure homogenization technique. In hot high-pressure homogenization, drug and lipids are melted and added to a surfactant solution to form a pre-emulsion which is then subjected to high-pressure homogenization and subsequently cooled form SLN. In cold high-pressure homogenization, drug and lipids are melted and then subjected to high-pressure homogenization at or below the room temperature. This is normally utilized for thermolabile drugs.

The second method of production of SLN is through microemulsions. [10] In this method, a hot microemulsion containing the lipids and surfactants is prepared and dispersed into cold water. Excess of water is removed by different techniques like lyophilization, and SLN is formed.

In emulsion formation-solvent evaporation method, [8] a lipid containing solution is emulsified with an aqueous phase and then solvent is evaporated, which leads to the precipitation of lipids and SLNs. Even double emulsification method can be used for the production of SLN. However, appreciation of size is a major concern while using this method.

SLN have also been synthesized with the help of high-speed stirring in combination with ultrasonication. This method is normally performed at higher temperatures. An advantage of using this method is that stirrers and sonicators are easily available and hence this method is cost effective. However, contamination with metal particles while performing probe sonication still remains one of the hurdles in this method.


   Applications of SLN in Medicine   Top


Topical administration

SLN can be effectively utilized for pharmaceutical products administered topically. They are made up of well-tolerated lipids and other excipients. Due to extremely small size, they have excellent adhesive properties on the skin, and hence its application for topical administration is enormous. In addition, with the help of SLN, the drug release can be controlled more effectively. SLN solid matrix also protected the active ingredients incorporated within them and thereby protected them from degradation. This was observed with active ingredients like retinol. SLN can also be used as a carrier system in cosmetics. SLN matrix can be used in sunscreens formulations. One of the biggest disadvantages of using sunscreen is its penetration into the skin, which eventually leads to irritation. It has been found that this penetration has decreased immensely while the sunscreen was formulated in a SLN matrix. In addition, SLN themselves were found to posses some sun protective effects. [11],[12] 

Parenteral administration

The advantages of SLN, as already discussed, make it suitable as a drug carrier through parenteral administration. They can be injected intravenously, intramuscularly, subcutaneously, or directly to the affected organ. Because of their extremely small size, they can be used systemically with very minimum risk of embolism. It has also been found that SLN are having very prolonged stability as long as 1 year. Various different drugs have been incorporated into the SLN system and intended for parenteral application. These may include anticancer drugs like paclitaxel and doxorubicin, antibiotics like tetracaine and tobramycin, CNS acting drugs like diazepam, to list a few. This shows the versatility of SLN to be drug carrier through parenteral administration in different therapies. [8] 

As a drug delivery system for proteins and peptides

Under prerequisite conditions, SLN can be used to incorporate and deliver both hydrophobic and hydrophilic proteins. The protein incorporated within SLN is free from exposure to external environment. Thereby, the proteins delivered through SLN avoid proteolytic degradation and their bioavailability is enhanced greatly. Various different proteins like cyclosporins, insulin, and somatostatin have been successfully incorporated within SLN matrix and studied. This system can be utilized then for different therapies through different routes of administration. These proteins or antigens can be incorporated within the SLN matrix or absorbed onto it. Even vaccines can effectively be administered with the help of SLN system. [13] 

Miscellaneous applications

In addition, SLN system can also be applied to deliver drugs through oral and pulmonary routes of administration. The final product may be dispersion or a traditional dosage form like tablets or capsules. For example, camptothecin-loaded SLN particles were successfully synthesized and stabilized with the help of stearic acid and poloxamer 188. [12] 

For more details please visit the website of CYS :http://www.cysonline.org/article.asp?issn=2229-5186;year=2011;volume=2;issue=1;spage=26;epage=28;aulast=Kokardekar

World Drug Delivery Congress 2011

 World Drug Delivery Congress is Asia Pacific's ONLY and MOST INFLUENTIAL drug delivery event!


In 2009, the drug delivery market was valued at US$101 billion and is forecast to increase about two-folds to an estimate of US$200 billion by 2016.

A recent research have revealed that the pharmaceutical industry is increasingly recognizing the importance of drug delivery innovations in order to help them address challenges such as the patent cliffs and heightened competition.

Against this backdrop, World Drug Delivery Congress 2011 will bring together multinational, specialty and generic pharmaceutical companies from Asia Pacific and globally to exchange ideas and debate on how to leverage on innovative drug delivery technologies to create more value in their product pipelines.

This is Asia Pacific region’s FIRST andHIGHEST LEVEL gathering that brings together more than 50 key decision makers in the pharmaceutical industry in a never been done before event. Discussions are set to range from the developments of innovative drug formulation and delivery strategies, to the ability to create new revenue streams and sustainable partnerships.

For more details, please visit the official website: http://www.imapac.com/index.php?page=world-drug-delivery-congress-2011

NDDS INDIA 2011- CONFERENCE

 The wide gap between the global and Indian NDDS industry presents a very lucrative oppurtunity to develop and capitalise upon the growing NDDS products market. Are you ready to meet the regulatory challenges,formulation and design rationales, scalability issues and marketing hurdles faced in order to grow and maintain your leadership in the NDDS industry?

CPhI is proud to announce its 2nd annual NDDS India conference on 11-12 August 2011 in Mumbai, India, designed specifically to prepare you for the challenges that lay ahead. Now a year older, and the only conference to focus on the niche NDDS market, NDDS India 2011 builds on the success of our 2010 programme and brings forward a revised, refreshed and solution-packed agenda that delves deeper into your every business issue. With the addition of a pre-conference seminar dedicated to showcasing the very latest international insights and developments around NDDS, this year’s event really is an opportunity not to be missed.

Fight the challenges and overcome the obstacles you face with the implementable will receive at this essential event through:

  • Panel discussions: Gain a clear overview of the next 4-5 years on development, approval and commerciality of NDDS projects
  • Plenary sessions: Benefit from the stimulating discussion of leaders in benchmark national and international pharma companies and key regulatory authorities
  • Power networking: Build bridges with your clients and peers and share insights like never before in the roundtable discussions
  • Product zone: Find solutions to your every need in the display zone and form partnerships to grow your business strategically

 

For more details, please visit the official site: http://ndds-india.com/

Dr L H Hiranandani Hospital in collaboration with International Oncology Centre opens cancer centre in Mumbai

 Mumbai based Dr L H Hiranandani Hospital today inaugurated its state of the art comprehensive cancer centre. The centre has been set up in collaboration with International Oncology Services a global cancer care and research company. 

The centre is equipped with the most advanced radiation therapy where the patient undergoes treatment for destroying the cancerous cells through radiation equipment RapidArc which reduces the time required for a patient to undergo radiation exposure to five minutes from the current twenty minutes. The centre also includes a bone marrow transplant facility which is a first of its kind in the private sector in Mumbai. The cancer centre was inaugurated by Suresh Shetty, state minister for Health, Maharashtra.

The radiation therapy technology at International Oncology centre is based on the ‘image guided radiotherapy’ (IGRT) platform which is the most advanced form of radiotherapy today. A compact advanced CT scanner helps make the most precise treatment possible. The Technology has an additional advantage of Intensity Modulated Radiation Therapy (IMRT), a high-precision radiotherapy that utilises computer-controlled x-ray accelerators to deliver precise radiation doses that can target tumours of varied shapes minimising the side effects. This result’s in sparing surrounding normal tissues accurately, which cannot be done effectively with other available technologies. In addition, with IMRT, a higher dose can be given to the tumour when the specified area is required to be targeted more accurately.

The bone marrow transplant (BMT) unit at Dr L H Hiranandani Hospital is a state of the art facility comparable to best of facilities across the globe and is geared for performing both autologous (related donar) and allogenic (non-related donar) transplants. Bone marrow transplant is a major treatment modality used for the management of various cancerous as well as non cancerous conditions. 

Since the patients have to be confined in their room for a long time, these rooms are not only specially designed for patient comfort but it is also ensured that patients do not develop infections due to microbes in the air. BMT unit have installed special filters called high efficiency particulate air (HEPA) filters to deliver purest air to the patients and centralized monitoring systems are installed in all the rooms for monitoring the patients closely. 

Highlighting the significance of the new cancer centre at Dr L H Hiranandani Hospital, Niranjan Hirandani, chief managing trustee of the hospital said, “The word ‘cancer’ brings to mind thoughts of a dreaded disease, whose growing incidence is a reality. Medical science is making rapid strides in the treatment of cancer, and India’s healthcare sector today has the infrastructure and technology comparable to the best in the world. Mumbai today has the best and latest treatment facility for cancer, and we are happy to make a difference in the treatment for cancer patients.”

Discussing the treatment modalities for cancer, Pradeep Jaisingh, MD and CEO, International Oncology services, said, “International Oncology is committed to bringing world class cancer care to India through latest technology expertise and its strategic collaboration with Albert Einstein College of medicine.”

According to Dr Suresh Advani, noted oncology expert, “Image guided radiotherapy is the fourth generation and the latest in radiation therapy technology. It helps to exactly locate the area where radiation is to be focused. Both in terms of patient safety and efficacy, Mumbai now has the best that is available anywhere in the world.”

Dr Sujit Chatterjee, chief executive officer, Dr L H Hiranandani Hospital said, “Healthcare facilities in metros like Mumbai have geared up to tackle the growing incidence of cancer. Earlier for complex treatments, patients had this perception of going abroad for treatment. Now, we have facilities for treating disease like cancer which are comparable to the best in the world.”

 

Source: Pharmabiz         Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62456&sid=2

Health ministry sets up task force to develop software for drug mfg & tracking system

 Aiming to find a software that could be used for tracking the drugs right from the manufacturers to the retailers to check the menace of counterfeiting of drugs in the country, the union health ministry has constituted a task force under the chairmanship of H G Koshia, commissioner, Food & Drugs Control Administration (FDCA), Gujarat. 

This task force was set up during a meeting that was held in Delhi in mid-March.

Once this task force submits its recommendation to the health ministry  they would take up this issue with the appropriate body. Once it is implemented in the country all the manufacturers in the country will have to adopt the new software and the state drug authorities will be liable to keep a tab on the companies and to check whether it is implemented effectively. 

H G Koshia, commissioner, Food & Drugs Control Administration (FDCA), informed, “We have members from across the sector to give their views and recommendation on the requirements for the software for drug manufacturing tracking system and how to track the medicines and control the issue of spurious drugs in the country. Our main aim is to ensure that all the drugs that are dispatched from the manufacturers would be traceable so that we can ensure that they are not counterfeited till they reach the retailers.” 

Koshia will be acting as the chairman of the task force where he will be assisted by nine other members from different ministries and from the drug control office.  As of now five members have been appointed in this task force. They are Dr Jagshetty, Karnataka Drugs Controller, Malai Mitra, deputy DCGI, Dr S Eswara Reddy, assistant drug Controller of India, Vishwajeet Ringe, senior technical director at NIC and one person from the CDSCO office. The other members will soon be appointed and they would be representatives from Department of Consumer affairs, Department of legal affairs, Department of Commerce; and one representative from the Department of health and family welfare.

Koshia informed that the task force will have its first meeting as soon as the rest of the members are finalised by the government. “We would discuss among ourselves on the issues and come out with consensus on requirements for the software for drug manufacturing tracking system and how to go about with its implementation. We would then recommend it to the government for further proceedings. Apart from having discussion on the requirements, we would also have sessions on the possibility of implementing  e-governance across the country as it is being followed in the state of Gujarat,” he informed.

 

Source: Pharmabiz          Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62459&sid=1

Lupin gets USFDA nod for metformin hydrochloride extended-release tablets 500mg & 1000mg

 Pharma major Lupin Ltd. announced that its US subsidiary, Lupin Pharmaceuticals Inc (LPI) has received tentative approval for its metformin hydrochloride extended-release tablets of 500mg and 1000mg strengths from the US Food and Drug Administration.

Lupin’s metformin hydrochloride extended release tablets are the AB rated generic equivalent of Andrx Labs LLC’s Fortamet 500mg and 1000 mg tablets. Fortamet is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Annual sales for Fortamet in the US was $83 million for the twelve months ending December 2010 as per IMS Health data.

Lupin believes that it is the first applicant to file an ANDA for Fortamet 500mg and 1000 mg containing a paragraph IV certification under the provisions of Hatch-Waxman Act. Upon receiving final approval by the FDA, Lupin believes that the 500 mg and 1000 mg strengths of its product will be entitled to 180 days of marketing exclusivity.

Vinita Gupta, CEO, LPI stated “We are happy to receive this approval. This product approval demonstrates our commitment to enhance our generic pipeline leveraging our development and manufacturing strengths in  extended-release dosage forms.”

 

Source: Pharmabiz            Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62476&sid=2

Keryx's Japanese partner begins phase 3 programme of ferric citrate to treat patients with hyperphosphatemia

 Keryx Biopharmaceuticals, Inc.announced that its Japanese partner, Japan Tobacco Inc. (JT) and Torii Pharmaceutical Co., Ltd. (Torii), JT's pharmaceutical business subsidiary, has commenced the phase 3 clinical programme of ferric citrate in Japan for the treatment of patients with hyperphosphatemia. 

Under the license agreement with JT/Torii, within 30 days, Keryx will receive a non-refundable milestone payment of $5 million from JT/Torii for the achievement of this milestone. Zerenex (ferric citrate), a ferric iron-based phosphate binder, is also in phase 3 clinical development in the United States for the treatment of hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease on dialysis. 

Ron Bentsur, chief executive officer of Keryx, stated, "We congratulate our partner, JT/Torii, on the initiation of the phase 3 programme in Japan and are excited by their progress. We believe that this serves to further validate the commercial potential for Zerenex worldwide." 

Keryx holds a worldwide license (except for certain Asian Pacific countries) to Zerenex from Panion & BF Biotech, Inc. 

In September 2007, Keryx sublicensed to JT and Torii the exclusive rights for the development and commercialization of its hyperphosphatemia drug, Zerenex (ferric citrate), in Japan. The licensing arrangement calls for JT and Torii to pay to Keryx up to $100 million in up-front license fees and payments upon the achievement of specified milestones, of which $28 million has been received by Keryx to date. In addition, upon commercialization, JT and Torii will make royalty payments to Keryx on net sales of the drug in Japan. JT and Torii are responsible for all development and commercialization costs in Japan. 

Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important pharmaceutical products for the treatment of cancer and renal disease. 

Source: Pharmabiz              Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62473&sid=2

Tuesday, April 19, 2011

US FDA seeks additional clinical data from Lilly's liprotamase NDA to treat exocrine pancreatic insufficiency

Eli Lilly and Company has received a complete response letter from the US Food and Drug Administration (FDA) for its New Drug Application (NDA) for liprotamase, a non-porcine pancreatic enzyme replacement therapy (PERT), under investigation for the treatment of exocrine pancreatic insufficiency (EPI).

The complete response letter communicated the need for Lilly to conduct an additional clinical trial prior to a re-submission.

"Lilly is looking forward to further discussion with the FDA to address the items outlined in the letter and provide the requested information as quickly as possible," said Eiry Roberts, M.D., Vice President, Autoimmune, Bone-Muscle-Joint, Liprotamase Product Development at Lilly.  "We are committed to working with the Agency and the cystic fibrosis community to make this important treatment option available to patients."

People with EPI have very low levels or none of the key digestive enzymes made by the pancreas - lipase, amylase and protease - in their small intestine, resulting in improper digestion and absorption of fat, carbohydrates and proteins, often requiring treatment with PERTs. EPI occurs very frequently in patients with cystic fibrosis (a life-threatening genetic disorder) and in other diseases including chronic pancreatitis and pancreatectomy.

Liprotamase is an oral, non-porcine (not made from harvesting the pancreas of pigs), biotechnology-derived, pancreatic enzyme replacement therapy (PERT) developed to treat patients with EPI associated with cystic fibrosis, chronic pancreatitis and pancreatectomy.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations.

 

Source: Pharmabiz           Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62430&sid=2

 

 

ICMR to begin research on antimicrobial resistance

In order to generate scientific evidence on the prevailing trends of antimicrobial resistance in the country and at all levels including primary, secondary and tertiary health care systems, the Indian Council of Medical Research (ICMR) will soon begin research on antimicrobial resistance.

Senior officials in the ICMR said that it is extremely essential to generate scientific evidence on the prevailing trends of antimicrobial resistance in all parts of the country and at all levels i.e. primary, secondary and tertiary health care systems. It is also vital to understand the unknown mechanisms of drug resistance in various micro-organisms. On individual basis, researchers have been reporting the presence of multi-drug resistant organisms and their anti-microbial susceptibility patterns, but there is lack of a consolidated effort to bring about a change.

It is under this background that the ICMR has decided to initiate research on antimicrobial resistance, the officials said.

The research projects will be mainly in the areas like microbial factors, host factors, environmental factors, ecological factors, improved diagnosis, etc.
 
Under the microbial factors, the study will focus on the genetic analysis of microbes to determine sequences of genes and reveal vulnerable areas in a microbe’s genome which could be used as potential drug targets or aid in the development of better diagnostic tests. It will also focus on mechanisms of emergence and transfer of resistance genes among pathogens in vivo (in the host), and the distribution and dissemination of specific antimicrobial resistance genes over time.

Under the host factors, the research will focus on vitro studies to determine the host factors and immune modulators (e.g. cytokines) in normal flora, serving as resistance determinants to antibiotics; and in-vivo correlations between resistance determinants in normal flora and the prevalence of resistant pathogens.

In the environmental factors, the study will focus on contamination of water and soil by pesticides, heavy metals and anti-bioticresidues and its relationship to drug resistance. In the ecological factors, it will focus on the role of normal flora and probiotics in the emergence/control of drug resistance.

The ICMR also proposes to network the existing centres of excellence working on drug resistance in individual microbes so that they follow standard protocols and institute quality assurance and quality control measures so that authentic data on prevalence and time trends could be generated. They would need to be equipped, trained and supported to start genetic level studies in development of drug resistance. The study in this area will focus on developing methods for early diagnosis and detection of resistant strains and molecular applications for the rapid diagnosis of difficult to treat (MDR-TB, XDR-TB) as well as common infectious diseases related infections causing URTI and diarrhoea. In such cases, the irrational use of antibiotics remains to be highest.

The ICMR also proposes study on improvement of existing treatment modalities and development of new treatment modalities.

 

Source: Pharmabiz     Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62437&sid=1

Amarin's AMR101 phase III anchor trial meets all primary and secondary endpoints

Amarin Corporation plc a clinical-stage biopharmaceutical company with a focus on cardiovascular disease, reported positive, statistically significant top-line results from its Anchor trial for the company's lead product candidate, AMR101. The phase III trial met its primary and secondary efficacy endpoints for both the 4 gram and 2 gram daily doses.

The purpose of the Anchor trial was to demonstrate that AMR101 is effective in reducing triglyceride levels in patients with high triglycerides without increasing LDL-C (bad cholesterol) levels in patients on background statin therapy. The Anchor trial investigated AMR101 as a treatment for high triglycerides (=200 and <500mg/dL) in 702 patients with mixed dyslipidemia (two or more lipid disorders) on background statin therapy at LDL-C (Low-Density Lipoprotein Cholesterol) goal who were at high risk of cardiovascular disease.

The majority of these patients were diabetic (73%). This is the largest trial with omega-3 therapy conducted in this important patient population. All patients were on background statin therapy with simvastatin, atorvastatin or rosuvastatin. Despite the benefits of statin therapy, patients in this population have significant residual risk for cardiovascular events.

The trial's primary endpoint was defined as the percentage change in triglyceride levels from baseline compared to placebo after twelve weeks of treatment. In addition, the study was powered to demonstrate a lack of LDL-C elevating effect with AMR101 compared to placebo. The trial was conducted under a Special Protocol Assessment (SPA) agreement with the FDA.

The primary endpoint for triglyceride change was achieved at both 4 grams and 2 grams per day with median placebo-adjusted reductions in triglyceride levels of 21.5% and 10.1% for the 4 grams and 2 grams per day dose groups, respectively. These reductions were both statistically significant (p<0.0001 and p = 0.0005, respectively). The median baseline triglyceride levels were 259 mg/dL, 265 mg/dL and 254 mg/dL for the patient groups treated with placebo, 4 grams and 2 grams of AMR101 per day, respectively. Even greater reductions in triglycerides were noted with higher potency statin regimens. Results were positive and statistically significant in both the diabetic and non-diabetic patient groups.

The trial's key secondary endpoint was to demonstrate a lack of elevation of LDL-C in order to avoid offset to the primary target of cholesterol lowering therapy. The trial's non-inferiority criterion for LDL-C was met at both AMR101 doses. The upper confidence boundaries for both doses were below the pre-specified +6% LDL-C threshold limit. In fact, at the 4 gram dose the upper confidence boundary was below zero (-1.7%) and at the 2 gram dose the upper confidence boundary was close to zero (0.05%). Moreover, for the 4 grams per day AMR101 group, LDL-C decreased significantly by 6.2% from baseline versus placebo, demonstrating superiority over placebo (p=0.0067). For the 2 grams per day group, LDL-C decreased by 3.6% from baseline versus placebo (p=0.0867).

In addition, the Anchor trial demonstrated statistically significant decreases in all predefined secondary endpoints at both doses studied. These endpoints were non-HDL-C, Apo B (Apolipoprotein B), Lp-PLA2 (lipoprotein phospholipase A2) and VLDL-cholesterol. Non-HDL-C decreased in the 4 grams per day group by 13.6% (p<0.0001) and in the 2 grams per day group by 5.5% (p=0.0054) compared to placebo. These are important lipid biomarkers as they represent predictors of cardiovascular risk. Apo B is a sensitive index of residual cardiovascular risk and is generally considered to be a better predictor than LDL-C. Lp-PLA2 is an enzyme found in blood and atherosclerotic plaque; high levels have been implicated in the development and progression of atherosclerosis. The safety profile of AMR101 was similar to placebo and there were no treatment-related serious adverse events in the trial. These results confirm and build upon the positive results for the Marine phase III trial announced in November 2010. The company expects to present more details of these results at an upcoming scientific meeting.

“The design and execution of the Anchor trial were robust and the trial results were very clearly positive,” said Christie M Ballantyne, MD, Methodist DeBakey Heart and Vascular Centre, Houston, and principal investigator of the Anchor trial. “I am very impressed with the performance of AMR101. In particular, whereas current triglyceride-lowering drugs may raise LDL-C and causes patient treatment concerns, AMR101 demonstrated a decrease in LDL-C beyond the decrease created by statin therapy. Furthermore, it is very encouraging for patient care that AMR101 caused reductions in significant markers of cardiovascular risk such as Apo B and non-HDL-C. The greater triglyceride reduction in patients with higher potency statin regimens is also very encouraging.”

Commenting on the Anchor trial results, Joseph S Zakrzewski, chief executive officer and executive chairman of Amarin, stated, “We are delighted by the results of the Anchor trial. In November we announced Marine trial results which position AMR101 to be best-in-class for treating patients with very high triglycerides. The Anchor trial results are even more remarkable than the broadly positive Marine trial results. We believe these results clearly differentiate AMR101 from other triglyceride lowering therapies and position AMR101 to be both first-in-class and best overall therapy for treating the high triglyceride population. We thank the Anchor team, including our investigators, for their many contributions to this outstanding study design and execution.”

In the US alone, approximately 40 million people have triglyceride levels above 200 mg/dL. The majority of these patients have high triglyceride levels of =200 and <500mg/dL as studied in the Anchor trial with approximately 4 million of these people having very triglyceride levels >500 mg/dL as studied in the Marine trial. Currently, no omega-3 based product is approved for the indication studied in the Anchor trial. In the seven largest pharmaceutical markets (US, Japan and five largest European markets), it is estimated that over 100 million people have mixed dyslipidemia.

The Anchor trial, a multi-centre, placebo-controlled, randomized, double-blind, 12-week pivotal study to evaluate the efficacy and safety of 2 grams and 4 grams of AMR101, enrolled 702 patients with fasting triglyceride levels from 200 mg/dL to less than 500 mg/dL who were also on background statin therapy (treated to the National Cholesterol Education Programme Adult Treatment Panel III (NCEP III) target goal of 100 mg/dL). Patients in this trial were characterized as having high triglyceride levels according to the NCEP III treatment guidelines. The secondary endpoints in the Anchor trial include the difference in LDL-cholesterol levels between AMR101-treated and placebo-treated groups to demonstrate that the addition of AMR101 to statin therapy does not increase LDL-cholesterol (LDL-C or bad cholesterol) in this population. Both treatment groups received statin therapy for the treatment of high LDL-cholesterol. Secondary measures in the Anchor trial were the difference in other lipid and biomarker levels between AMR101 and placebo treatment groups.

The three background statins used in the Anchor trial, simvastatin, atorvastatin or rosuvastatin, represent approximately 80% of statins currently used. The most common trade names for these drugs are Zocor, Lipitor and Crestor, respectively.

AMR101 is a prescription-grade omega-3 fatty acid, comprising not less than 96% ultra pure icosapent ethyl (ethyl-EPA), that Amarin is developing as a potentially best-in-class prescription medicine for the treatment of patients with very high triglyceride levels (>500 mg/dL) and as a potentially first-in-class therapy for patients with high triglyceride levels (>200 and <500mg/dL) who are also on statin therapy for elevated LDL-cholesterol levels. Significant scientific and clinical evidence support the efficacy and safety of ethyl-EPA in reducing triglyceride levels.

Amarin Corporation plc is a clinical-stage biopharmaceutical company with expertise in lipid science focused on the treatment of cardiovascular disease.

  Source: Pharmabiz           Website link:  http://www.pharmabiz.com/NewsDetails.aspx?aid=62442&sid=2


TRTB to launch blue diamond pill targeting ethnic market with sexual enhancement pills

True 2 Beauty Inc., a leading distributor of male and female sexual potency pills and liquid products in the United States, is pleased to announce the launch of a new, additional line of sexual enhancement supplements for men and women under the brand Blue Diamond (for men) and Pink Diamond (for women). The pills are already being sold online as well as at retail; product began shipping in the past few weeks.

“We believe segmenting the market by creating targeted product brands, will allow growth across all demographics. Our flagship brand, Libigrow, although widely distributed, has been mostly focused on a mainstream audience; with Blue Diamond we believe we have created a look and feel that provides a clear differentiation. The packaging and website will be provided in multiple languages. There are many retail locations that serve a wide array of ethnic backgrounds. We strongly support the concept that we can have competing brands within the same retail location,” states Alex Hbaiu, its CEO.

The company believes Blue Diamond sales should exceed $500,000 in its first 12 months, which should be accretive to existing Libigrow and Libigirl sales. The company will evaluate the need to seek celebrity endorsements for the Blue Diamond brand as the line becomes more widely distributed. Currently, the line is sold directly to regional distributors by the company.  “We are currently developing other lines of products, some of which may be appropriate under the umbrella of the Blue Diamond brand,” continues Hbaiu.

Management is reporting anticipated 2nd quarter sales, which end April 30, should be in line with the company's internally planned forecast. Further, it is anticipating announcing shortly a very exciting opportunity that can potentially be another significant component of our future growth. This information will be released during an upcoming conference call which will be announced in the coming weeks.

True 2 Beauty Inc. is a leading distributor of male and female sexual potency pills and liquid products in the United States. The True 2 Beauty line of current products includes Libigrow, Libigirl, Blue Diamond, Pink Diamond, LibiShots, and the Relaxation Drink.

 

Source: Pharmabiz         Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62444&sid=2

NIH researchers complete whole-exome sequencing of skin cancer

Study is the most comprehensive view of melanoma’s genetic landscape. A team led by researchers at the National Institutes of Health is the first to systematically survey the landscape of the melanoma genome, the DNA code of the deadliest form of skin cancer. The researchers have made surprising new discoveries using whole-exome sequencing, an approach that decodes the 1-2 per cent of the genome that contains protein-coding genes. The study appears in the April 15, 2011, early online issue of Nature Genetics.

Melanoma is the most serious form of skin cancer and its incidence is increasing faster than any other cancer. A major cause is thought to be overexposure to the sun, particularly ultraviolet radiation, which can damage DNA and lead to cancer-causing genetic changes within skin cells.

“It is now clear that genomic analysis will have a major impact on our ability to diagnose and treat cancer,” said National Human Genome Research Institute Director Eric D Green, MD, PhD “This study represents a collaboration of basic science, clinical research, genome sequencing and data analysis at its best.”

The researchers conducted a comprehensive genome analysis and explored the melanoma genome’s functional components, especially gene alterations, or mutations. They studied advanced disease — the metastatic stage — when cells have the highest accumulation of gene mutations.

“Melanoma is one of the most challenging solid cancers to work with because it has such a high rate of mutation,” said senior author Yardena Samuels, PhD, investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research. “Whole-exome sequencing will help us identify the most important changes.”

NHGRI researchers and a colleague from the Johns Hopkins Kimmel Cancer Center in Baltimore designed and analyzed the new study, while National Cancer Institute (NCI) researchers and colleagues from the University of Texas MD Anderson Cancer Centre in Houston and the University of Colorado Denver School of Medicine collected melanoma tumour samples.

“This study is an example of the vital utility of preserving high-quality tumour samples that include clinical information,” said study co-author Steven Rosenberg, MD, PhD, chief of surgery at the NCI. “Furthermore, it is a powerful example of the importance of bridging basic science and clinical medicine.”

As a first step in the study, NHGRI researchers obtained 14 metastatic melanoma tumour samples and matching blood samples from a collection maintained at NCI. Whole-exome sequencing of the 28 samples was performed at the NIH Intramural Sequencing Centre.

The exome sequence data required a number of analytic steps to separate functionally important mutations from a large number of total results. The first of these analyses differentiated the mutations that occur sporadically in the tumour, called somatic mutations, from inherited mutations. It entailed a comparison between the mutations observed in the blood samples and those from the tumour cells of the same individual. Researchers eliminated from further analysis any tumour mutations that also occurred in normal tissue.

Within that large set of somatic mutations, the sequence contained thousands of mutations that occur but are presumed to have no role in tumour development, called passenger mutations, since they likely are just along for the ride. Researchers derived a rate for occurrence of passenger mutations versus driver mutations, known as the background mutation rate. This statistic differs for each cancer type. In their study, the authors provide the most comprehensive data to date about this aspect of melanoma mutation analysis.

The researchers excluded from further analysis any inherited genetic alterations already annotated in such datasets as the Single Nucleotide Polymorphism database, or dbSNP, and the 1,000 Genomes Project. Additionally, bioinformatic analysis looking at genes conserved across species suggested which mutations were worth additional functional investigation. “Most of the mutations are passenger mutations, which means they don’t have a functional role in melanoma,” Dr Samuels said.

Once the passenger mutations were ruled out, the team could focus on those most likely to cause melanoma. The researchers identified 68 genetic changes that appeared to be somatically mutated at elevated frequency. They then identified 16 genes deemed to be melanoma driver mutations, factoring for both the background mutation rate and the numbers of respective mutations found in the tumours in this study. Of the 16, only the oncogene BRAF had ever been implicated in melanoma.

The ionotropic glutamate receptor gene, GRIN2A, was the most highly mutated of the genes newly implicated in melanoma. It contained mutations in 33 percent of an NCI sample set and in 25 percent of a larger set of samples that combined those maintained by NCI and two other collections. The researchers suggest that this gene is important because of its role in the signalling pathway. “There are some indications that suggest that this is a tumour-suppressor gene,” Dr Samuels said, “but we still need to prove that using functional studies.” Tumour-suppressor genes typically act like a brake, preventing uncontrolled cell growth characteristic of cancer.

Next, the researchers looked for recurrent, or hot-spot, mutations that occurred in multiple patient tumours. The BRAF gene with a hotspot mutation previously implicated in melanoma led a list of nine additional genes with mutations that occurred in more than one tumour. Mutations in seven of the nine genes caused protein-coding changes. These seven hot-spot mutations led the researchers to look precisely for these mutations in 153 additional melanoma tumours.

Mutations in one particular gene, known as TRRAP, emerged as remarkable for occurring at the exact position in six separate individuals with melanoma. TRRAP harbours a recurrent mutation clustered in one position along the string of DNA code in about 4 percent of cases.

“These data suggest that TRRAP is a driver and probably an oncogene,” said Dr Samuels. Oncogenes are cancer-causing genes that enable the cell to survive despite stressful conditions, rather than die off normally. “This was one of the most important discoveries in the study since we never expected to identify novel hot-spot mutations,” she said.

TRRAP is found in many species, suggesting its importance in normal function and that mutations in this gene would detrimentally affect protein function. To confirm a possible cell-survival function for TRRAP, the researchers disrupted the gene in mutant cell lines. The cells had an increase in cell death over time. Cancer cells normally fail to undergo cell death, which allows them to become immortal and cause disease. The test showed that TRRAP is a cancer-causing oncogene, because the mutant cell is clearly dependent on it. Dr Samuels cautioned that while this discovery is exciting, it remains a basic science finding and does not necessarily suggest a therapy.

Lastly, the researchers used cell signalling pathway analysis, identifying glutamate signalling as a pathway involved in melanoma. “We are starting to explore what mutations do to the glutamate pathway,” said Dr Samuels, noting that ongoing research will entail complex biochemistry. She added that NIH colleagues published a study in the April 21, 2003, issue of Nature Genetics almost exactly eight years ago, implicating the glutamate signalling pathway in melanoma.

“This work demonstrates that our intramural researchers are on the front line of genomics and bioinformatics, providing high quality data and analysis to address important questions about health and disease,” said NHGRI scientific director Daniel Kastner, MD, PhD.

As part of their sequencing analysis, NISC investigators developed a statistical tool named Most Probable Genotype. The tool calculates reliability of data produced in the sequencing process. “This paper is not only about biology,” said Dr Samuels. “We are providing an effective tool for the other researchers who conduct exome sequencing so they too are able to validate which DNA alternations are reliably detected.”

NHGRI is one of the 27 institutes and centres at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases.

NCI leads the National Cancer Programme and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers.

NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the US Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Source: Pharmabiz           Website link: http://www.pharmabiz.com/NewsDetails.aspx?aid=62441&sid=2

Monday, April 18, 2011

MSD India launches pentavalent rotavirus vaccine in India