Drug-Eluting Peripheral Stent Continues to Show Positive Data at Two Years

Patients treated with the Zilver® PTX™ Drug-Eluting Peripheral Stent maintained clinical improvement at two years, according to interim results from the Zilver® PTX™ Global Registry presented today as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 33rd Annual Scientific Sessions. The prospective, single-arm study is ongoing to evaluate the drug-eluting stent for the treatment of peripheral artery disease (PAD). Results of a separate pivotal randomized study in a similar cohort of patients are expected to be available later this year.

In the meantime, this analysis includes 12-month follow-up data from 721 patients and 24-month follow-up data from 447 patients who received the Zilver® PTX™ paclitaxel-coated stent in the superficial femoropopliteal artery (SFA), a major artery above the knee. The registry study was designed to evaluate stent integrity, event-free survival and freedom from target lesion revascularization.

PAD affects more than eight million people in the U.S. and, if not treated, can limit the ability to walk and exercise, as well as place patients at risk for limb loss. PAD patients also have a greater chance of heart attack, stroke and death.

Although use of DES is common in the coronary arteries, the peripheral arteries, including those in the legs, experience different types of stress caused by walking and other movement. In some instances, blockages in these arteries are very difficult to treat, and may ultimately lead to limb amputation. The study is the third to evaluate the effectiveness of a drug-eluting stent outside of the coronary arteries, but the first to suggest clinical efficacy. The Zilver® PTX™ is an investigational device.

The characteristics of the 787 patients who were enrolled and treated included restenosis of previously treated lesions in 24 percent, in-stent restenosis in 14 percent, and total occlusions in 38 percent; 22 percent of patients had lesions longer than 15 cm. The mean lesion length was 10.0 +/- 8.2 cm, the mean percent diameter stenosis was 84.6 +/- 16.4 percent, with an average of 2.2 Zilver® PTX® stents used per patient.

At 12 months, the event-free survival rate was 87.0 percent, and freedom from target lesion revascularization was 90.5 percent. X-ray evaluation found a very low rate of stent fractures, 1.5 percent of patients at 12 months. Patients available for 24-month follow-up had an event-free survival rate of 80.0 percent, and freedom from target lesion revascularization was 83.3 percent.

This low rate of target lesion revascularization translated into meaningful clinical improvement for the majority of patients, with both the average walking distance and average walking speed more than doubling following Zilver PTX stent implantation, and being sustained to two years. In addition there was a very good safety profile, and a very low rate of stent fractures.

"These interim data suggest this device is safe and efficacious for the treatment of SFA lesions," said William A. Gray, M.D., FSCAI, who presented the study data and is associate professor of clinical medicine and director of endovascular services at Columbia University Medical Center/New York Presbyterian Hospital. "Prior attempts to demonstrate drug-eluting stent effectiveness using sirolimus or its analogues have fallen short, but the use of a paclitaxel-coated, non-polymeric stent appears to have improved the outcomes for patients who received this study stent. If these results are confirmed in the separate randomized study using the same device, it will be welcome news to patients who suffer from this disease."

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Parents Try Alternative Treatments for Autism

Many families are turning toward to special diets and/or psychotropic medications to help better manage autism spectrum disorder and its symptoms in their children, two new studies show.

The CDC estimates that about one in 110 children in the U.S. have an autism spectrum disorder, the umbrella name given to a group of disorders that can range from the mild to the severe that often affect social and communication abilities.

One study shows that 21% of children with autism spectrum disorder are using complementary and alternative medical therapies. Of these, 17% were on special diets, most commonly a gluten-free or casein-fee diet.

Another study shows that more than one-quarter of children with autism spectrum disorder receive at least one psychotropic medication to treat some of their behavioral symptoms such as hyperactivity or irritability.

Both studies were presented at the Pediatric Academy Societies annual meeting in Vancouver, British Columbia, and were sponsored by the Autism Treatment Network, a network of 14 centers across the U.S. and Canada that is focused on developing standards of care for treating children with autism spectrum disorder.

"Complementary medicine is used for all sorts of things such as arthritis and attention deficit hyperactivity disorder (ADHD), so to see it being used for children on the spectrum is pretty much expected," says Daniel Coury, MD, chief of developmental behavioral pediatrics at Nationwide Children's Hospital in Columbus, Ohio, and the medical director of the Autism Treatment Network.

"Families may be looking at complementary treatment because traditional medical treatments may not be doing the job for their child," he says. There is some anecdotal evidence that these diets may improve symptoms among some children with autism.

Parents need to make sure that their child's doctors are aware of what they are taking as some alternative therapies may have side effects on their own or when used in combination with other therapies, he says.

Psychotropic Medications

The study shows that younger children with autism were less likely than older kids to receive psychotropic medications. Sixty percent of children aged 11 and older took one psychotropic drug, compared with 44% of children aged 6 to 10, 11% of children ages 3 to 5, and 4% of children under age 3. The most commonly used medications were stimulants to help treat ADHD symptoms and a drug called risperidone, which is prescribed to treat irritability. Older children were more likely to be taking more than one psychotropic drug, the study shows.

The study raises some questions about how, when, and even why these medications are being used in autism treatment, Coury says.

"It may be that parents and doctors are not treating these children when they are first diagnosed, which usually occurs at very young ages," Coury says. But "as the diagnosis is established, there is a higher likelihood of medications being prescribed. Or the use of these drugs may reflect those children who are more severely affected or don't have access to other nonmedical treatments such as intensive behavioral therapies," he says.

Children who are diagnosed with autism often see numerous specialists several times a week for various types of speech and behavioral therapy.

But "if these therapies are not available, parents may reach for plan B or plan C," he says.

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Drug-laser combination proves effective for diabetic blindness

A study shows that combining the drug ranibizumab, or Lucentis, with laser therapy is twice as effective at improving vision for those with diabetic macular edema.

For the first time in a quarter of a century, researchers have identified a new treatment for diabetic macular edema, a potentially blinding disorder that affects about 1 million Americans, researchers said Tuesday.

The treatment uses a drug called ranibizumab, which when administered in combination with laser phototherapy is twice as effective at reversing vision loss as laser therapy alone. Laser therapy to prevent leakage of blood vessels in the retina has been the gold standard since it was introduced in 1985. The findings were reported online in the journal Ophthalmology.

Nearly 50% of those who received both the drug and phototherapy had a visual improvement of at least two lines on an eye chart, compared with 28% of those receiving only phototherapy, researchers found. And only about 5% of those receiving both therapies had further deterioration of vision, compared with 14% of those receiving just phototherapy.

"This will have a major impact on how ophthalmologists will treat macular edema in people with diabetes," said Dr. Neil M. Bressler of the Wilmer Eye Institute at Johns Hopkins University, who led the study. The drug, sold under the brand name Lucentis, is already approved for treatment of macular degeneration, and physicians can use it off-label to treat macular edema, he said.

Macular edema is a form of diabetic retinopathy, which is the most common cause of vision loss in working-age Americans. It is marked by leakage of small blood vessels in the retina, the light-sensitive portion of the eye.

When fluid accumulates in the center of the retina — the macula — the condition is called macular edema. Increased pressure damages the cells, impairing vision. Because the macula is the most important part of the retina for reading, driving and recognizing faces, macular edema can be severely disabling.

Ranibizumab, manufactured by the biotech company Genentech, is what's known as a monoclonal antibody — a protein created to bind to a molecule in a specific way. Injected into the eye, it slows leakage by blocking the receptor for a hormone called vascular endothelial growth factor, or VEGF.

Bressler's team studied 691 diabetics at 52 clinical centers. Some had both eyes treated, for a total of 854 eyes. Patients were divided into four groups — receiving either ranibizumab plus prompt laser treatment, the drug plus delayed laser treatment, laser treatment plus an injected steroid called triamcinolone, or laser treatment plus a sham injection.

After a year of follow-up, nearly 50% of those receiving Lucentis had a visual improvement of two lines on a vision chart, meaning they could read letters that were at least a third smaller than they could read before the study. It didn't matter whether laser treatment was prompt or deferred.

About 28% of those receiving laser treatment alone or in combination with triamcinolone had a similar improvement. But though there were very few complications related to Lucentis — primarily infections associated with the injection — about 30% of those receiving triamcinolone developed high intraocular pressure requiring treatment, and 60% developed cataracts requiring surgery.

The trial was funded by the National Eye Institute, but Genentech donated the expensive drug and contributed $9 million to the cost of the trial.

After earlier small studies suggested that such treatment could benefit macular edema patients, some ophthalmologists have been using Genentech's anti-cancer drug Avastin, which also blocks VEGF receptors, to treat the condition macular edema because it is much cheaper. It costs less than $100 per dose, compared with about $2,000 for Lucentis, and the eye institute has been criticized for testing Lucentis rather than the cheaper drug.

Dr. Frederick L. Ferris III, the institute's clinical director, acknowledged at a news conference that Genentech's financial contributions to the trial had swayed the decision-making process.

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New treatments address unmet needs in Alzheimer's and epilepsy

A number of leading drug makers used this year's meeting of the American Academy of Neurology to present new data for promising pipeline candidates. Despite promising results, however, Datamonitor believes that the epilepsy drugs will struggle to find their place in the market. Moreover, the positive Phase II data for Baxter’s potential Alzheimer’s therapy Gammagard do not guarantee later success.

Alzheimer's disease: hope remains despite setbacks

There remains an enormous unmet need in the treatment of Alzheimer's disease. For the millions of elderly people worldwide, there are just four drugs available that can only offer a modest symptomatic effect. Even so, these treatments cannot slow or modify the course of this neurodegenerative disease, which is the ultimate goal in Alzheimer's therapy. While it was announced in March 2010 that in a Phase III trial Medivation/Pfizer's Dimebon (latrepirdine) failed to meet any of its clinical endpoints, there remains hope in the pipeline for Alzheimer's sufferers and their caregivers. One such drug, Baxter's Gammagard (intravenous immune globulin; IGIV), is actively recruiting for a Phase III trial, and at the American Academy of Neurology Annual Meeting (AAN 2010) the company presented new data from the extension phase of its Phase II trial.

Gammagard is a human antibody preparation already launched for the treatment of primary immunodeficiency diseases in the US and Western Europe. The drug is currently being assessed in Phase III clinical trials in patients with mild-to-moderate Alzheimer's disease. At AAN 2010, Baxter presented clinical trial results for the first time measuring function and cognition in patients who received uninterrupted Gammagard for a period of 18 months for mild-to-moderate Alzheimer's disease. After 18 months, patients who received Gammagard continuously averaged approximately 1.36 points higher than patients who initially received placebo on the Alzheimer's disease Cooperative Study-Clinical Global Impression of Change rating (ADCS-CGIC).

While clarifying that the study involved only a very small number of patients, Baxter is clearly encouraged by these data and has stated that it plans to initiate a second, concurrent Phase III study of the drug in this patient population. However, in light of the recent setback with Dimebon and other numerous late-stage trial failures in the last 10 years, Datamonitor remains cautious about Gammagard's prospects until Q3 2011 when results of the 360-patient Phase III study are expected.

Epilepsy: long-term data for new drugs the highlight

The second half of 2008 and first half of 2009 saw a flood of generic second-generation anticonvulsants enter the US market as Lamictal (lamotrigine; GlaxoSmithKline), Keppra (levetiracetam; UCB), Depakote IR and ER (valproate semisodium; Abbott) and Topamax (topiramate; Johnson & Johnson) lost patent protection. As the market environment for new and prospective drug candidates becomes increasingly price-sensitive and competitive, both Valeant/GlaxoSmithKline and UCB presented long-term safety and efficacy data for their respective novel anti-epileptic candidates in order to support their positions in the growing treatment arsenal.

Valeant's retigabine is a first-in-class anti-epileptic drug that reduces neuronal excitability by enhancing the activity of neuronal KCNQ (Kv7) potassium channels and through its gamma aminobutyric acid type A (GABA-A) receptor agonistic properties. In August 2008, Valeant entered into an exclusive worldwide collaboration agreement for retigabine with GlaxoSmithKline, and in October 2009 the companies filed a New Drug Application (NDA) in the US and a Marketing Authorization Application (MAA) in Europe for the adjunctive treatment of partial-onset seizures in adults with refractory epilepsy.

The efficacy and safety of retigabine in patients with refractory partial-onset epilepsy was demonstrated in two pivotal Phase III trials, RESTORE 1 and RESTORE 2. At AAN 2010, Valeant provided insight into the maintenance of efficacy and the safety profile of retigabine at doses of 600mg-1,200mg/day, as demonstrated in the long-term open-label extensions of the trials. With 81% of patients transitioning from RESTORE 1 and 92% doing so from RESTORE 2, median percent reduction in 28-day total partial-seizure frequency was 57% and 53%, respectively. Furthermore, safety assessments supported what Valeant called an acceptable safety profile for an adjunctive therapy.

With both US and EU regulatory bodies currently appraising the drug, Datamonitor believes that the inconvenient dosing regimen and reasonably high level of treatment-related side effects will deter some treatment-refractory epilepsy patients and their physicians from using retigabine, despite the strong efficacy data demonstrated thus far.

UCB's Vimpat (lacosamide) was the subject of numerous studies and analyses at this year's AAN conference. Indicated as an adjunct therapy for the treatment of partial-onset seizures in adults with epilepsy, Vimpat was approved in the EU in September 2008 and shortly after in October in the US, making it one of the most recent novel entrants to the epilepsy market. Although monotherapy trial data is anticipated by mid-2011, long-term analysis from adjunct trials presented on the conference provides additional support to Vimpat's growing safety and efficacy profile.

Data presented during the meeting focused largely on providing long-term safety/tolerability and efficacy of Vimpat from Phase II-III double-blind and/or open-label extension trials. While one study reported the efficacy of Vimpat in cohorts of patients completing successively longer durations of lacosamide exposure, another indicated that lacosamide improved 50% responder rates and reduced median seizure frequencies by up to 42% and 86% for complex partial seizures and secondarily generalized seizures (the two most commonly reported seizure types), respectively. A third poster provided insight into the drug's long-term safety profile; an important consideration for a drug dosed in such a chronic fashion.

However, with questions previously raised regarding the drug's side-effect profile in comparison to first-line treatments like levetiracetam and lamotrigine, Vimpat is likely to encounter difficulty in taking significant market share from its well-tolerated competitors. Datamonitor predicts that potential future indication expansions in pediatric patients as well as primary generalized tonic-clonic seizures will hold the key for Vimpat's commercial success in epilepsy.

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New malaria pill matches Novartis drug in study

A new drug for malaria proved as effective as Novartis's leading treatment Coartem in a clinical trial, researchers said on Friday, although an outside expert said the findings had limitations.
Coartem is the current "gold standard" for people infected with the mosquito-borne disease. The two-in-one Novartis drug needs to be taken twice a day and requires a fatty diet for optimum absorption.

Pyramax from South Korean drugmaker Shin Poong Pharmaceuticals is taken just once daily.

A randomized Phase III study of Pyramax -- a fixed-dose combination of pyronaridine and artesunate -- showed a treatment response of 99.5 percent compared to 99.2 percent among patients on Coartem, which combines artemether and lumefantrine.

Researchers involved in the study wrote in the Lancet medical journal that a three-day course of Pyramax should be considered for inclusion in malaria treatment programs, especially given its low cost of less than $1 for adults and 50 cents for children.

In an accompanying comment, however, Dr Francois Henri Nosten of the Mahidol-Oxford University Tropical Medicine Research Programme said a limitation of the study was that it consisted of many older African children and adults who had probably acquired some malaria immunity.

He also raised concerns about patients on Pyramax having raised liver enzymes, a possible signal of liver toxicity.

The Pyramax study was sponsored by Shin Poong and the non-profit Medicines for Malaria Venture (MMV).

MMV argues it is vital to have multiple anti-malaria drugs available to ensure innovation and guarantee competition in the marketplace, thereby driving down prices for life-saving medicines in poor countries.

Pyramax was submitted to the European Medicines Agency for regulatory approval earlier this year.

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Promising New Treatment For Heart Failure

An anti-depressant drug developed over 40-years ago has been found to dull, even reverse muscle enlargement and weakened pumping function connected to heart failure, in animal experiments carried out by a team of researchers from Johns Hopkins.

Publishing their report in the journal Circulation Research, the heart experts describe how the no longer in use anti-depressant clorgyline, blocked enzyme monoamine oxidase-A (MAO-A) from breaking-down a key neurohormone in a dozen key laboratory experiments on rodents. The enzyme norepinephrine is responsible for controlling the the pace of blood pumping and in response to stress, it makes the heart pump harder and faster.

These findings are the first evidence showing how elevated MAO-A activity that bio-chemically drives heart failure can be stalled by drug therapy.

Insomnia, agitation, high blood pressure after ingesting foods containing the amino acid tyramine, a protein that stimulates a surge of stored stimulatory hormones, specifically, norepinephrine are some of the notable side effects from clorgyline.

Patients taking clorgyline and whose chemical binding to MAO-A is irreversible, should avoid tyramine-rich foods, such as, chocolate, red wine, certain beans, aged cheeses and meat.

An estimated 5.7-million American men and women suffer from chronic heart failure, which killed an estimated 290,000 people in 2005.

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New Pathways In The Treatment Of Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related mortality in both men and women in the United States and throughout the world. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Sadly, most cases of lung cancer are diagnosed at an advanced stage, conferring a poor prognosis.

Should Phase III results be positive, the next step is filing a New Drug Application, for eventual FDA approval. Occasionally Phase IV trials are run, to evaluate the side effects, risks, and benefits of an already approved drug over a longer period of time, and in a larger number of people than in phase III clinical trials.

Typical first-line therapy (the initial treatment used) for advanced NSCLC patients in the United States is paclitaxel plus carboplatin. There are many possible side effects including nausea, increased risk of infection, anemia, and hair loss. Carboplatin can cause kidney damage, while paclitaxel can cause aching joints and muscles, and lowered blood pressure.

An examination of Phase III clinical trials published from 2001-2008 reveals that the one-year survival rate for patients receiving paclitaxel and carboplatin first-line therapy was on average only about 40%, the weighted average for median survival was 9.7 months, and the objective tumor response (defined as greater than 30% tumor shrinkage) rate was about 27%.

Could the efficacy of these agents be improved, and the side effects lessened? Novelos Therapeutics, Inc., a New England-based biopharmaceutical company [www.novelos.com], certainly thinks so. The company's lead product, NOV-002, is presently in a Phase III clinical trial, with top-line trial results expected later in the first quarter of 2010.

NOV-002 acts in conjunction with paclitaxel plus carboplatin as a chemopotentiator and a chemoprotectant. Thus, NOV-002 makes the chemo more effective, while lessening the side effects. NOV-002 is already approved in Russia, where excellent results have been observed. Related Russian Phase II trials demonstrated that NOV-002 increased the one-year survival of advanced NSCLC patients from 17% to 63%, and improved tolerance of chemotherapy.

Additional studies suggest that NOV-002 efficacy is not limited to particular types of tumors, or chemotherapy agents.

Novelos president and CEO Harry Palmin is enthusiastic. "We are on track for our pivotal Phase III trial to conclude this quarter. "Should this registrational trial be positive, we will proceed with filing a New Drug Application (NDA) in 3Q 2010. Thereafter, based on our Fast Track designation, we would project FDA approval for first-line treatment of advanced NSCLC in combination with chemotherapy in 1Q 2011."

Other promising new approaches in chemotherapy involve attaching the drugs to monoclonal antibodies, which could afford benefits in efficacy and reduction of side effects. These antibodies can be designed to bring the chemo agent directly to the tumor. Similar benefits are said to occur with liposomal therapy, whereby the drugs are packaged inside liposomes (synthetic fat globules).

With annual diagnoses of NSCLC in the United States approaching 200,000 and the annual death toll close to 150,000 any improvements in therapy are surely welcomed, but we still have a long way to go.

Michael D. Shaw
Exec VP
Interscan Corporation

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Novartis biological drug Ilaris® approved in EU to treat Cryopyrin-Associated Periodic Syndrome

The new biological medicine Ilaris® (canakinumab) has been approved in the European Union (EU) to treat adults and children as young as four years old with cryopyrin-associated periodic syndrome (CAPS), a rare life-long auto-inflammatory disease with debilitating symptoms and few treatment options.

The accelerated EU decision follows approvals in the US and Switzerland, where Ilaris was granted priority review in view of the significant unmet medical need. Ilaris is the only medicine approved in the EU for CAPS patients as young as four years old, and for patients with the most debilitating form of CAPS, neonatal-onset multisystem inflammatory disease (NOMID)[4]. It is a fully human monoclonal antibody given by injection under the skin once every two months - the longest dosing interval of any available treatment .

"We are excited by the latest approval because Ilaris represents a significant therapeutic advance for patients with this debilitating and sometimes fatal disease," said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. "Ilaris is the outcome of our pathways-driven search for innovative medicines that are tailored to the needs of patients. Initially we studied Ilaris in a very rare disease with a well-understood genetic profile, and now that its efficacy has been proven, we are able to move ahead rapidly with development in other diseases characterized by the same inflammatory process."

The regulatory submission was supported by data showing that Ilaris produced rapid and sustained remission of symptoms in up to 97% of CAPS patients, with most of them responding within hours of the first injection .

Ilaris, previously known as ACZ885, targets and normalizes the production of a protein within the immune system called interleukin-1 beta (IL-1ß). In CAPS patients, IL-1ß is overproduced causing widespread inflammation and tissue damage . Symptoms, such as debilitating fatigue, fever, joint pain and conjunctivitis, can be present from infancy and continue throughout the patient's life .

If left untreated, CAPS may have serious consequences such as deafness, bone deformities, erosive joint destruction, and central nervous system damage leading to loss of vision . Around 25% of patients develop amyloidosis, a condition in which the build-up of proteins can cause vital organs to fail, resulting in renal failure and requiring kidney transplantation. Approximately 20% of patients with NOMID, the most severe form of CAPS, die before reaching adulthood .

CAPS is believed to occur in around one in 2,500 people in the EU[3],[11], but fewer than 1,000 cases have been reported worldwide due to poor diagnosis[1],[3]. CAPS includes three distinct autoinflammatory disorders of increasing severity: familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID[2],[3]. Ilaris is the only treatment indicated in the EU and Switzerland to treat all three disorders .

Studies with ACZ885 are ongoing in other diseases in which IL-1ß plays an important role, such as chronic obstructive pulmonary disease (COPD), type 2 diabetes, systemic juvenile idiopathic arthritis (SJIA), and gout - one of the most painful forms of arthritis. Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.

The CAPS filing was based on a clinical trial program involving more than 100 patients. Data from a pivotal study published in The New England Journal of Medicine show that Ilaris produced a rapid, complete and sustained response in most patients.

None of the patients treated with Ilaris (0 out of 15) experienced a disease outbreak or 'flare' compared to 13 of the 16 patients who received placebo (0% vs. 81% respectively, p<0.001).>"In CAPS studies, symptoms improved within 24 hours after patients received a single dose of Ilaris. The disease was barely detectable in the blood after two weeks and the remission of symptoms was sustained for six months," said Helen J. Lachmann, MD of the UK National Amyloidosis Centre at the Royal Free and University College Medical School in London, UK. "By effectively turning off the disease activity, Ilaris has the potential to transform patients' lives by offering long-term control of their disease."

Ilaris was generally well tolerated and there was no consistent pattern of adverse events apart from a slight increase in infections . Two patients experienced serious adverse events, namely a lower urinary tract infection and vertigo .

The most common adverse events were nasopharyngitis, diarrhea, influenza, headache and nausea . Ilaris was not associated with any severe injection-site reactions and those that did occur were classified as mild-to-moderate .

The EU approval was granted under exceptional circumstances, a common practice with so-called orphan drugs. This reflects a need for additional data due to factors such as the rarity of the disease or lack of scientific knowledge. The situation is reviewed every year until the European Medicines Agency (EMEA) is able to grant a normal approval. In addition to its orphan drug status for CAPS, Ilaris has been designated as an orphan drug for treating SJIA, the most severe form of arthritis in children, in the US, EU and Switzerland, and has fast-track status for SJIA in the US. Orphan drugs are those developed to treat diseases affecting fewer than 200,000 people (in the US) or fewer than five out of 10,000 people (in the EU).

Ilaris was approved in Switzerland in July 2009 to treat all three forms of CAPS in adults and children over four years old, and in the US in June 2009 to treat two forms of CAPS, namely FCAS and MWS, while a study in NOMID patients is under way. Priority reviews are ongoing in other countries including Australia, Brazil and Canada.

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First Drug For Scleroderma Treatment Maybe on Horizon

Until now, no drug has been found to be effective for treating scleroderma. Results of a new study to be presented at the annual meeting of the American College of Rheumatology in Philadelphia on October 18 may change that.

Approximately 300,000 people in the United States have scleroderma, a chronic connective tissue disease in which hardening of the skin is one of the most obvious signs. Scleroderma can also affect other areas of the body, including the blood vessels, lungs, kidneys, heart, and gastrointestinal tract. The disease can range in severity from mild to life-threatening, which depends on where and to what extent the disease develops.

Scleroderma affects women about four times more than men, and it typically first appears between the ages of 30 and 50. No cure has been found, and treatment consists of medications to relieve symptoms that can range from heartburn to itchy skin, dry mouth, skin fibrosis, pulmonary fibrosis (lung disease), depression, joint and muscle pain, and Raynaud’s syndrome.

The potential new treatment for scleroderma is Gleevec (imitinib mesylate), a drug that is currently approved to treat certain types of cancer. In the study, which was conducted by investigators at Hospital for Special Surgery, 30 patients with severe scleroderma were given 400 mg of Gleevec daily. Patients were evaluated every month for one year and monitored for three months after stopping the drug.

The investigators evaluated how much of the skin was affected by the disease and also measured lung function, as lung disease is the main cause of death among people with scleroderma. After one year of treatment, the patients had a 23 percent improvement in skin scores and improvements in lung function ranging from 9.6 to 11 percent. The improvement in lung function is especially important, as this aspect of scleroderma typically worsens over time. In this study, however, the patients improved in two vital lung tests: forced vital capacity and diffusion capacity.

Further studies of the use of Gleevec in the treatment of scleroderma need to be conducted. Part of that effort and other research of scleroderma may be facilitated by passage of the “Scleroderma Research and Awareness Act,” a bill (H.R. 2408) that was introduced to the United States Congress in May 2009 and that is still accepting sponsors.

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New Compound Fights Tumors

An experimental cancer drug that switches off the so-called "Hedgehog" pathway beat back tumors in more than half of patients with advanced basal cell carcinoma, a type of skin cancer.

The drug also helped a 26-year-old man suffering from medulloblastoma, the most common form of brain cancer in children.

"We were both pleased and surprised. We had hoped that we might see responses like this but we in no way anticipated that, within the context of a phase 1 clinical trial, we would see this level of anti-tumor activity," said Dr. Charles M. Rudin, who authored two papers on the findings that appear in the Sept. 2 online edition of the New England Journal of Medicine. "These are the first reports in the literature of any Hedgehog inhibitor being used clinically."

Phase 1 trials are conducted to look at a drug's safety profile and determine the right dose. Phase 2 and phase 3 trials typically look at effectiveness.

Also exciting, however, is the fact that the Hedgehog pathway has been implicated in other cancers, notably colon cancer and ovarian cancer, albeit in a different way.

Researchers are going forward to look at the potential of the molecule, known as GDC-0449, to treat these types of cancers as a one-drug regimen, and in combination with other drugs for other solid tumor malignancies, said Rudin, who is associate director for clinical research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.

One expert noted that finding a compound that might control the Hedgehog pathway could have far-reaching implications.

"These are phase 1 trials so they're quite preliminary, but the drug is quite effective in at least a subset of the patients treated," said Dr. Andrzej Dlugosz, author of an accompanying editorial and a professor in the department of dermatology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor. "The reason we're so excited is that there are now a large number of cancers that have also been linked to abnormalities in this pathway, including pancreatic, colon, ovarian and prostate. It's quite an impressive list. The data is pretty strong suggesting that if you shut down the pathway, it can have a pretty profound effect on those tumor cells. If it can work in these cancers, maybe it can work in other cancers, even though the signaling there is more complex."

But another researcher warned that it is premature to get too excited about the results.

"It's great to see something with so much potential, but it really is potential," said Dr. Clifford Perlis, director of Mohs Micrographic Surgery and Dermatologic Surgery at Fox Chase Cancer Center in Philadelphia.

However, he added, "there are other companies developing Hedgehog inhibitors as well, so I think people should be paying attention to this."

The Hedgehog gene, so named because it was first discovered in flies with hair resembling the spikes of hedgehogs, "is really important during early embryonic development in pretty much all animal species from flies to mice to humans, and for pretty much every tissue you can imagine," explained Frederic de Sauvage, also an author on both papers. "But remarkably in adults, it seems to be mostly turned off."

De Sauvage is vice president of research, molecular biology, at Genentech, which developed the molecule and funded the study.

Some 1 million Americans get basal cell carcinoma each year. It often doesn't spread but, once it has, there are no approved treatments. Medulloblastoma is an aggressive form of brain tumor.

The first trial enrolled 33 individuals whose basal cell carcinoma had spread locally or to distant organs.

Half of the participants who had distant metastases saw a reduction in tumor size, as did 60 percent of those with locally advanced cancer. The rest had either stable or progressive disease after 10 months of follow-up.

But "stable" in this population may not mean much, Perlis pointed out, as it is generally a very slow-growing cancer.

The man with medulloblastoma also saw a significant shrinkage of his tumor, along with vastly improved quality of life, but only for two months. He later died.

A third study by some of the same authors, this one published online Sept. 2 in Science Express, discovered that treatment with GDC-0449 actually spurred another mutation in a gene called SMO, which caused the brain tumor to become resistant to the drug.

Because the Hedgehog pathway does not actually do much in adults, side effects were minimal, said de Sauvage.

GDC-0449 would likely be used very differently, depending on which type of cancer it is targeting.

In the case of basal cell carcinoma and medulloblastoma, the mutation in the Hedgehog pathway "really drives the formation of these tumors," de Sauvage said. "This molecule inhibits the pathway very specifically and, to date, we only know of these two types of tumor where the pathway is mutated." That means GDC-0449 is effective on its own.

But in colon and ovarian cancer, he continued, the pathway recruits surrounding cells to promote the cancer. In these types of tumors, GDC-0449 would have to be combined with other drugs.

Source : www.empowher.com

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Old Drugs Combine to Produce New Weight Loss Benefit

The maker of an investigational diet drug -- actually a combination of a drug used to treat alcohol dependence and an antidepressant -- said the combo produced significant weight loss in three clinical trials.

In the concurrent trials with 4,500 obese patients, those given bupropion/naltrexone (Contrave) daily for 56 weeks lost at least 5% of body weight, the FDA benchmark for efficacy of diet drugs, according to a statement from drug maker Orexigen Therapeutics of San Diego.

Bupropion is an antidepressant marketed under the name Welbutrin that is also used as a smoking cessation aid under the name Zyban. Naltrexone is an opioid receptor antagonist used to treat drug and alcohol dependence.

The company said it planned to file a New Drug Application with the FDA during the first half of 2010.

The findings were unveiled during a teleconference with reporters at 8 a.m. EDT, well before the opening of the markets in New York -- the company's stock trades on Nasdaq.

The COR trials (Contrave Obesity Research) randomized patients to bupropion/naltrexone or placebo.

The COR I trial enrolled 1,742 obese patients to two active doses (bupropion 360 mg plus naltrexone at 16 mg or 32 mg) or placebo. After 56 weeks, patients randomized to the 32 mg naltrexone combination lost a mean of 8.1% of baseline body weight or about 18 pounds versus a loss of 1.8% of baseline body weight or four pounds in the placebo group (P<0.001).>

The results were similar in the COR II trial, which recruited 1,496 patients. A third trial examined the combination in patients with diabetes and found that those on active therapy lost a mean of 5.9% of baseline body weight or 13.5 pounds versus 2.2% and five pounds in the control group.

The company said that combined data from the three trials revealed that after 56 weeks of treatment mean blood pressure was unchanged among patients taking the combination, whereas controls had a slight decrease in blood pressure.

There was also a slight increase in pulse rate among patients randomized to bupropion/naltrexone.

Source : www.medpagetoday.com

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New strategy in tumor treatment

A new strategy proposed by researchers at Dartmouth Medical School and Amtek, Hanover, NH may treat tumors that do not respond to conventional treatment. The study, which was published on May 29th in the open access, peer reviewed journal PLoS ONE, uses a combination of two agents to selectively kill tumors while protecting healthy cells.

In previous studies, researchers discovered that a specific enzyme known as methylthioadenosine phosphorylase (MTAP) is missing in 35 to 70 percent of lung, pancreatic and biliary tract cancer, melanoma, glioblastoma, osteosarcoma, soft-tissue sarcoma, mesothelioma, and T-cell acute lymphoblastic leukemia. Although information on the incidence of MTAP-deficiency in breast cancer is still limited, researchers believe it is probably significant.1 Since the discovery of MTAP-negative tumors, there have been several proposals, over the years, to take advantage of the frequent absence of MTAP in so many lethal cancers. None of these proposals, however, has led to successful clinical use.

Dr. Martin Lubin, Professor of Microbiology, Emeritus, and co-author Adam Lubin of Amtek have offered a new approach. They say, “Our strategy consists of two agents. One drug is given that is toxic both to cancer cells and to normal host tissues. A second, but non-toxic, drug is also given, which protects normal tissues from the toxic action of the first agent. This two-drug combination therapy kills tumor cells while normal tissues are well protected.” They go on to state, “Among the drugs used to kill the tumor cells, two — thioguanine and fluorouracil (or its prodrug Xeloda) - are already in clinical use. In general, the dose of these drugs is limited by toxic side effects. However, with our strategy, greatly increased doses might be used and tumors not susceptible to low doses could be attacked successfully at higher doses, without harm to host tissues.”

To assess the selective killing of tumor cells when they were present in excess of normal cells, the researchers designed co-culture experiments in vitro and animal studies are now in progress.

“We hope that successful animal studies will lead to clinical application as soon as possible,” Dr. Lubin said.

Source : www.breakthroughdigest.com

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Novel Drug Discovery Tool Could Identify Promising New Therapies For Parkinson's Disease

Researchers have turned simple baker's yeast into a virtual army of medicinal chemists capable of rapidly searching for drugs to treat Parkinson's disease.

In a study published online July 13 in Nature Chemical Biology, the researchers showed that they can rescue yeast cells from toxic levels of a protein implicated in Parkinson's disease by stimulating the cells to make very small proteins called cyclic peptides. Two of the cyclic peptides had a protective effect on the yeast cells and on neurons in an animal model of Parkinson's disease.

"This biological approach to compound development opens up an entirely new direction for drug discovery, not only for Parkinson's disease, but theoretically for any disease where key aspects of the pathology can be reproduced in yeast," says Margaret Sutherland, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS). "A key step for the future will be to identify the cellular pathways that are affected by these cyclic peptides." This research was funded by the National Institutes of Health.

The research emerged from the lab of Susan Lindquist, Ph.D., a professor of biology at the Massachusetts Institute of Technology (MIT), a member of the Whitehead Institute for Biomedical Research, and a Howard Hughes Medical Institute investigator. Dr. Lindquist is also an investigator at the Massachusetts General Hospital (MGH)/MIT Morris K. Udall Center for Excellence in Parkinson's Research, one of 14 such centers funded by NINDS to develop treatment breakthroughs for Parkinson's disease. The study received additional funding from NIH's National Institute of Environmental Health Sciences, and from the Michael J. Fox Foundation and the American Parkinson's Disease Association.

Parkinson's disease attacks cells in a part of the brain responsible for motor control and coordination. As those neurons degenerate, the disease leads to progressive deterioration of motor function including involuntary shaking, slowed movement, stiffened muscles, and impaired balance. The neurons normally produce a chemical called dopamine. A synthetic precursor of dopamine called L-DOPA or drugs that mimic dopamine's action can provide symptomatic relief from Parkinson's disease. Unfortunately, these drugs lose much of their effectiveness in later stages of the disease, and there is currently no means to slow the disease's progressive course.

In most cases, the cause of Parkinson's disease is unknown, but there are recent, tantalizing clues. Investigators have discovered that vulnerable brain cells in patients with Parkinson's disease accumulate a protein called alpha-synuclein. Moreover, genetic abnormalities in alpha-synuclein cause a rare familial form of the disease. Dr. Lindquist and her team previously showed that when yeast cells are engineered to produce large amounts of human alpha-synuclein, they die.

In their new study, Dr. Lindquist and her team tested whether yeast could make cyclic peptides that would save them from alpha-synuclein's toxicity. Cyclic peptides are fragments of protein that connect end-to-end to form a circle. Although cyclic peptides are synthetic, they resemble structures that are found in natural proteins and protein-based drugs, including pain killers, antibiotics and immunosuppressants. Cyclic peptides that suppress alpha-synuclein toxicity could be candidate drugs for Parkinson's disease, or they could help researchers identify new drug targets for the disease.

"Our technique, which capitalizes on a long line of investigation in my lab, will lead to a whole new way to obtain small molecule tools useful for improving our understanding of disease mechanisms and for developing new therapies," says Dr. Lindquist. She notes that her lab and others have modeled many human diseases in yeast and in other kinds of cells.

Joshua Kritzer, Ph.D., a chemist and postdoctoral fellow in Dr. Lindquist's lab, designed and executed the cyclic peptide strategy. His procedure involves exposing yeast cells to short snippets of DNA that the cells can absorb and use to make cyclic peptides. Then, he flips the genetic switch that causes the cells to produce toxic levels of alpha-synuclein. If the yeast make cyclic peptides that suppress alpha-synuclein toxicity, they live; if not, they die. This simple assay enables testing millions of cyclic peptides simultaneously in millions of yeast cells. The process is extremely rapid and much less expensive compared to other techniques used to screen large number of chemicals with an eye toward new drugs.

"We are making the yeast do a ton of work for us. They make the compounds and then they tell us which ones are functional," Dr. Kritzer says. Out of a library of 50 million cyclic peptides, only two saved the yeast from alpha-synuclein toxicity.

Dr. Lindquist's team collaborated with other researchers to test these two cyclic peptides in C. elegans, a millimeter-long worm with a small number of dopamine-producing neurons that are easy to examine and count. Those neurons are vulnerable to alpha-synuclein toxicity, but they were less vulnerable and more likely to survive in worms that were genetically modified to make either of the two cyclic peptides. Guy Caldwell, Ph.D., and Kim Caldwell, Ph.D., professors of biology at the University of Alabama in Tuscaloosa developed this C. elegans model, and performed the testing.

The researchers have not yet determined why the cyclic peptides are protective. They found that the cyclic peptides do not affect a system of transport inside cells known as vesicle trafficking – which was a surprise, since alpha-synuclein and other proteins that have been implicated in human Parkinson's disease are believed to play a role in vesicle trafficking. However, the researchers observed that the two peptides share a structure that may hold clues to their targets.

"This protein structure has important biological functions," says Dr. Kritzer. It is found in a class of antioxidant proteins known as thioredoxins, in proteins that shuttle metals around a cell, and in proteins that regulate gene activity. The connection to antioxidants and to metals ties into other lines of research. NINDS is currently supporting clinical trials in patients to test whether specific antioxidants slow the progression of Parkinson's disease. High doses of heavy metals such as lead, manganese, iron and mercury are known to be toxic to brain cells.

The researchers are conducting further experiments to explore how cyclic peptides prevent cell death. They are also adapting their system for making cyclic peptides so that it can be used in other cell types (including human cells) and other diseases.

Source : www.sciencedaily.com

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Parkinson's medications may help treat extreme drug-resistant TB

Two drugs that are commonly used to treat Parkinson's disease have been found to be effective in treating extreme drug-resistant tuberculosis, say researchers at the University of California, San Diego.

They have discovered that the two commercially available drugs, entacapone and tolcapone, have the potential to treat multi-drug resistant and extensively drug resistant tuberculosis.

"We have computational, and experimental data to support this repositioning," said Dr Philip E. Bourne, professor of pharmacology at UCSD's Skaggs School of Pharmacy and Pharmaceutical Sciences and the principle investigator on the project.

"What is exciting about this finding is that the TB target, enzyme InhA, is already well known. But existing drugs are highly toxic and of completely different chemical structure than entacapone and tolcapone.

"Here we have drugs that are known to be safe and with suitable binding properties which can be further optimized to treat a completely different condition," he added.

While working with the TB bacterium itself, they found that the active component in Comtan tablets (entacapone) is effective at inhibiting M.tuberculosis in concentrations well below a level that is toxic to cells.

"Although we have demonstrated in the lab that Comtan is active against M.tuberculosis, additional studies are required in order to transform it into an anti-tubercular therapeutic," said Sarah L. Kinnings, a graduate student and lead author on the study.

"Given the continuing emergence of M.tuberculosis strains that are resistant to all existing, affordable drug treatments, the development of novel, effective and inexpensive drugs is an urgent priority," she added.

The study appears in PLoS Computional Biology.

Source : www.newkerala.com

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Controversial cancer stem cells offer new direction for treatment

In a review in Science, a University of Rochester Medical Center researcher sorts out the controversy and promise around a dangerous subtype of cancer cells, known as cancer stem cells, which seem capable of resisting many modern treatments.

The article proposes that this subpopulation of malignant cells may one day provide an important avenue for controlling cancer, especially if new treatments that target the cancer stem cell are developed and combined with traditional chemotherapy and/or radiation.

“The fact that these concepts are steadily making their way into the clinic is exciting, and suggests that the recent interest in cancer stem cells may yield beneficial outcomes in potentially unexpected ways,” wrote co-authors Craig T. Jordan, Ph.D., professor of Medicine at URMC and director of the James P. Wilmot Cancer Center Translational Research for Hematologic Malignancies program; and Jeffrey Rosen, Ph.D., the C.C. Bell Professor of Molecular and Cellular Biology and Medicine at Baylor College of Medicine.

Cancer stem cells (CSCs) are a hot topic in the scientific community. First identified in 1994 in relation to acute myeloid leukemia, CSCs have now been identified in several solid tumors in mice as well. Scientists who study CSCs believe they have distinct properties from other cancer cells, and may be the first cells to undergo mutations.

Research from the past 10 years suggests that because CSCs may be the root of cancer, they also might provide a new opportunity for a treatment. Jordan and a group of collaborators, for example, are testing a new drug compound based on the feverfew plant that demonstrates great potential in the laboratory for causing leukemia CSCs to self destruct.

Another new approach, the authors said, is the use of chemical screens to search drug libraries for already approved agents that may target CSCs, or make resistant tumor cells more sensitive to chemotherapy and radiation.

Cancer stem cell biologists hypothesize that any treatment that targets the source of origin rather than simply killing all cells, healthy and malignant, would be an improvement over most conventional therapies.

Some scientists, however, are uncertain if CSCs have unique biological properties or any relevance to treatment, the authors noted. What is more likely to fuel cancer, other studies have found, are unfavorable factors in the neighboring cells surrounding the tumor, such as mutated genes, proteins that encourage cell growth, and a poor immune system, for instance.

The most challenging issue facing CSC biologists is that the number and type of cancer stem cells can vary from patient to patient. In some tumor samples, for example, CSCs are rare while in others they constitute a large portion of the tumor mass, the authors said.

To understand why CSCs are so variable, investigators are trying to determine what genes and pathways are responsible for activating cancers that have a poor prognosis, and whether these cancers also have a higher frequency of CSCs.

“Whether the cancer stem cell model is relevant to all cancers or not,” they wrote, “it is clear that we need new approaches to target tumor cells that are resistant to current therapies and give rise to recurrence and treatment failure.”

An unexpected benefit of so much attention on normal stem cells is that it has stimulated research in areas not previously the focus of cancer therapies, Jordan and Rosen said.

For example, pathways known to be important for normal stem cell self-renewal, such as the Wnt, Notch and Hedgehog(Hh) pathways, are now of increased interest due to their potential role in CSCs. The first clinical trial using an agent to block the Notch pathway in combination with chemotherapy for breast cancer has begun.

The authors conclude by spotlighting the pressing need for preclinical models to test appropriate doses and combinations of CSC therapies before they can move into human clinical trials.

Source : www.lifesciencesworld.com

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Carb Synthesis Sheds Light on Promising Tuberculosis Drug Target

A fundamental question about how sugar units are strung together into long carbohydrate chains has also pinpointed a promising way to target new medicines against tuberculosis.

Working with components of the tuberculosis bacterium, researchers from the University of Wisconsin-Madison identified an unusual process by which the pathogen builds an important structural carbohydrate. In addition to its implications for human health, the mechanism offers insight into a widespread but poorly understood basic biological function — controlling the length of carbohydrate polymers.

“Carbohydrate polymers are the most abundant organic molecules on the planet, and it’s amazing that we don’t know more about these are made,” says Laura Kiessling, a professor of chemistry and biochemistry at UW-Madison. “There’s not much known about how length is controlled in these carbohydrate polymers.”

Kiessling is senior author, along with graduate students John May and Rebecca Splain and postdoctoral fellow Christine Brotschi, of a new study appearing in the online Early Edition of the Proceedings of the National Academy of Sciences the week of June 22.

Most carbohydrates exist as many sugar molecules linked into long chains, or polymers. The right number of sugars in the chain is vital for them to work properly, but different types of carbohydrate polymers range from a few dozen sugars in some bacterial molecules to tens of thousands of sugar links in cellulose, a common plant material.

Despite its importance, it's not clear how carbohydrate length is determined, Kiessling says. Unlike some biological chains — such as DNA and proteins — that are built off a template that guides the length of the final product, carbohydrate-synthesizing enzymes work without templates.

“Nature has strategies to generate polymers of different lengths, but we know very little about those strategies,” she says. “If you make something too short, it’s probably not going to function in the role that you want, and if you make something too long, you’re wasting energy that you need to use elsewhere.”

The research team focused on an enzyme called GlfT2 that is responsible for building a critical carbohydrate component of the TB bacterial cell wall.

The researchers found that a small fatty component at the starting end binds to the enzyme and helps it track the length of the growing polymer. As the enzyme adds more and more sugar units to the opposite end, the chain becomes increasingly unwieldy.

“If the chain gets too long, it gets hard to hold on to both of the ends, so the chain falls off” the synthesizing enzyme, Kiessling says, forming a completed carbohydrate polymer.

The researchers believe that the enzymes responsible for building different types of carbohydrates exceed their comfort level at different points, leading to molecules of different prescribed lengths.

The current report is the first description of this “tethering” mechanism — named for the fatty lipid that tethers the start of the polymer to the enzyme — in carbohydrate synthesis, Kiessling says, though it may prove to be common among other organisms as well.

In addition to providing insight into what may be a general mechanism for designing and building carbohydrates, the work gives insight into developing new therapeutics against TB. The GlfT2 enzyme is essential for bacterial survival and growth but has never yet been targeted by potential treatment methods. Knowing that the enzyme has two binding sites — one for each end of the growing carbohydrate — makes it an especially appealing candidate.

“Our mechanism provides a blueprint for strategies to block a new anti-mycobacterial target,” Kiessling says.

New drug targets will be critical in the fight against tuberculosis, as drug-resistant strains are becoming increasingly widespread. The carbohydrate-synthesizing enzyme represents an untapped and promising resource for crippling even strains that are resistant to current drugs.

The prevalence of carbohydrate polymers in biological systems also means that understanding how their length is controlled has many possible applications, ranging from designing more potent and effective vaccines to facilitating the production of useful fuels from plant materials.

“It’s a nice illustration of how basic research can lead to applications that are very practical,” says Kiessling.

The research was funded by the National Institutes of Health, National Science Foundation, American Chemical Society and Swiss National Science Foundation.

Sourec : www.newswise.com

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Strativa's New Drug Application For Ondansetron Orally Dissolving Film Strip Accepted By FDA

Strativa Pharmaceuticals, the proprietary products division of a wholly owned subsidiary of Par Pharmaceutical Companies, Inc. , today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for ondansetron orally dissolving film strip (ODFS). Strativa is seeking approval of ondansetron ODFS for the prevention of nausea and vomiting associated with highly- and moderately-emetogenic chemotherapy, radiotherapy and surgery.

The ODFS, a new oral formulation of ondansetron designed to rapidly dissolve on the tongue, was developed using MonoSol Rx' proprietary PharmaFilm(TM) thin film technology. In clinical studies, this formulation demonstrated bioequivalence to ondansetron orally disintegrating tablets (ODT), both with and without water. Pursuant to Prescription Drug User Fee Act (PDUFA) guidelines, Strativa expects the FDA will complete its review or otherwise respond to the NDA by the first quarter of 2010.

"We are very pleased with the acceptance of our NDA submission and look forward to cooperating with the FDA on its review," said John A. MacPhee, President, Strativa Pharmaceuticals. "We believe the quick dissolving film strip formulation of ondansetron offers a convenient and easy-to-administer option for managing nausea and vomiting associated with chemotherapy, radiotherapy and surgery."

Nausea and vomiting is a common side effect associated with chemotherapy, radiation and surgery. Left untreated, nausea and vomiting can have serious consequences such as exhaustion, dehydration and undernourishment, which can interfere with treatment and healing.

In June 2008, Strativa and MonoSol Rx entered into an exclusive licensing agreement under which Strativa acquired the U.S. commercialization rights to ondansetron orally dissolving film strip.

About Strativa Pharmaceuticals

Strativa Pharmaceuticals is the proprietary products division of Par Pharmaceutical, Inc. Strativa is committed to developing and marketing novel prescription drugs. Its initial focus is on supportive care therapeutics in HIV and oncology. Drawing on the specialty products expertise of its staff, Strativa possesses the resources to prepare products for commercialization and to help ensure their success after launch.

About Par Pharmaceutical

Par Pharmaceutical, Inc. develops, manufactures and markets generic drugs and innovative branded pharmaceuticals for specialty markets.

Safe Harbor Statement

Certain statements in this news release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. To the extent any statements made in this news release contain information that is not historical, these statements are essentially forward-looking and, as such, are subject to known and unknown risks, uncertainties and contingencies, many of which are beyond the control of the Company, which could cause actual results and outcomes to differ materially from those expressed herein. Risk factors that might affect such forward-looking statements include those set forth in Item 1A of the Company's Annual Report on Form 10-K for the year ended December 31, 2008, in other of the Company's filings with the SEC from time to time, including Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, and on general industry and economic conditions. Any forward-looking statements included in this news release are made as of the date hereof only, based on information available to the Company as of the date hereof, and, subject to any applicable law to the contrary, the Company assumes no obligation to update any forward-looking statements.

Source : www.medicalnewstoday.com

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FDA approval requested for Crestor-Trilipix combo

The pharmaceutical industry's latest proposed merger wasn't about turning two companies into one but about uniting two widely used dyslipidemia drugs in a single pill. Abbott Laboratories and AstraZeneca have asked the FDA to approve a combination of their products fenofibric acid (Trilipix) and rosuvastatin (Crestor), respectively, for the treatment of mixed dyslipidemia, the companies have announced . If they get their wish, the product will be sold as Certriad.

In December, as reported by heartwire, Trilipix became the first fibrate to be approved for use with a statin, although in actual practice the two drug classes are frequently combined.

Together, rosuvastatin and fenofibric acid can reduce high LDL-cholesterol and triglyceride levels and raise low HDL cholesterol. The companies note that their application to the FDA "is supported by data from multiple studies, including efficacy and safety studies with the 5-mg, 10-mg and 20-mg doses of rosuvastatin combined with fenofibric acid."

In a separate announcement, the two companies said they have agreed to "copromote" Abbott's Trilipix within the US for monotherapy or in combination with a statin .

Source : www.theheart.org

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New drug cocktail brings hope to leukemia cancer patients

Using an asthma medication already available on the market, scientists were able to treat chronic myeloid leukemia by targeting a gene involved with the inflammatory response.
Specifically, the gene Alox5 was found to play a vital role in the development and maintenance of cancer stem cells. Normally, “it processes essential fatty acids to leukotrienes, which are important agents in the inflammatory response.”

The researchers found that chronic myeloid leukemia (CML) did not develop in mice without Alox5 because of impaired function of leukemia stem cells. Also, Alox5 deficiency did not affect normal stem cell function, providing the first clear differentiation between normal and cancer stem cells.

Using this knowledge, the team treated CML mice with two already-available prescription medications: Zileuton and Gleevec (imatinib). Zileuton, an asthma medication, was chosen because it inhibits the Alox5 inflammation pathway. Imatinib is a leukemia medication. Combined, the two drugs “provided an even better therapeutic effect.”

The research is published in the journal Nature Genetics, and is authored by Shaoguang Li, M.D., Ph.D., et al. of the University of Massachusetts Medical School in Worcester.

Source : www.digitaljournal.com

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ImmunoCellular Therapeutics Reports Additional Data from Promising Brain Cancer Clinical Trial

ImmunoCellular Therapeutics, Ltd. , a biotechnology company, presented promising clinical data from a Phase I trial evaluating ICT-107, the company's dendritic cell-based cancer vaccine product candidate for the treatment of glioblastoma. These data were reported at the American Society of Clinical Oncology Meeting in Orlando, Florida (Abstract #2032), and supplement the preliminary data from the completed clinical trial that the Company reported in December 2008.

The Phase I clinical trial of ICT-107 was conducted to evaluate the safety and tolerability of the cancer vaccine in patients with glioblastoma, the most common and malignant type of brain cancer. The trial enrolled 19 patients—16 with newly-diagnosed and three with recurrent disease—and was conducted at Cedars-Sinai Medical Center.

Seven of the 16 newly-diagnosed patients demonstrated stable disease with median progression-free survival of 64 weeks, and three of these seven patients have progression-free survival of over two years. The median progression-free survival time of newly-diagnosed glioblastoma patients is historically 30 weeks. ICT-107 was well tolerated, and no significant adverse events were reported. Nine of the 16 newly-diagnosed patients had progressive disease with a median progression-free survival of 39 weeks and median survival of 56 weeks. The three patients enrolled who had recurrent disease progressed in their disease but still exhibited extended survival times of 34, 47 and 59 weeks.

Fifteen patients in the trial were evaluated for immune responses, and six of them had a significant immune response to at least one tumor-associated antigen. Patients demonstrating an immune response are exhibiting a trend toward longer overall survival. ICT-107 was well tolerated in the study, with no grade 3/4 adverse events and only mild side effects, including grade 1 fatigue, skin rash and pruritis, which were transient in nature.

“The survival benefit that we are seeing in this trial of ICT-107 is exciting. As a physician who regularly treats glioblastoma patients, having access to an immunotherapy like ICT-107, which may someday have the ability to provide patients with an extended survival and a relatively innocuous side effect profile would be a great improvement over what we currently have to offer,” stated Surasak Phuphanich, M.D., the principal investigator of the trial and a senior author of the ASCO presentation. “With a historical median progression-free survival time of 6.9 months in glioblastoma, we are encouraged to see a median progression-free survival time of 14.2 months (57.5 weeks) in this newly-diagnosed glioblastoma (16 patients) population, and furthermore, it is exciting to see the correlation between immune response and survival given that the goal of ICT-107 is to elicit a cancer-specific immune response.”

“While the data from ICT-107 are encouraging, our top priority is to advance our 'off-the-shelf' cancer stem cell vaccine product candidate, ICT-121, into the clinic. IMUC is expecting to file an Investigational New Drug (IND) application for ICT-121 in the fourth quarter of this year. ICT-121, which may have applicability to multiple types of cancer, will target glioblastoma in the initial Phase I trial,” stated Manish Singh, Ph.D. “With the great unmet need represented by glioblastoma across all age groups, we are hopeful that an immunotherapy, such as ICT-121 or ICT-107, may someday offer patients a more effective and safer treatment alternative.”

About ICT-107

ICT-107 is IMUC's patient-specific therapeutic cancer vaccine product candidate that consists of dendritic cells—immune system cells responsible for presenting antigens (immune system targets) to the immune system—which are obtained from the patient's blood and “programmed” with tumor antigens which in turn provide a target for the immune system. The immune system should then be armed to seek and destroy any remaining glioblastoma cells. Patients in the Phase I trial received three intradermal injections of ICT-107 at two-week intervals.

About Glioblastoma

The high rate of mortality of patients diagnosed with brain cancers and in particular with glioblastoma multiforme (the most lethal and devastating form) is driving the scientific community to discover and develop improved treatments that could increase the survival time and enhance the quality of life of patients. Of the approximately 19,000 cases of malignant brain and spinal cord tumors that are diagnosed each year in the United States, there currently is no satisfactory treatment, and the two-year survival rates are only in the range of 26 percent. Neither surgery, radiation nor anti-cancer drugs, the standard treatment modalities, have shown to date any prospect of meaningful extension of patients' lives.

About ImmunoCellular Therapeutics, Ltd.

IMUC is a Los Angeles-based clinical-stage company that is developing immune based therapies for the treatment of brain and other cancers. The company's “off the shelf” therapeutic vaccine product candidate targeting cancer stem cells for multiple cancer indications is targeted by IMUC to enter clinical trials during the fourth quarter of 2009. IMUC has recently completed a Phase I trial of its dendritic cell-based clinical product candidate for glioblastoma. IMUC is in pre-clinical development of a monoclonal antibody product candidate for the treatment of small cell lung cancer and pancreatic cancer, and is also evaluating its platform technology for monoclonal antibody discovery using differential immunization for diagnosing and treating multiple types of cancer. To learn more about IMUC, please visit www.imuc.com.

Forward-Looking Statements

This press release contains certain forward-looking statements that are subject to a number of risks and uncertainties, including without limitation, the risks associated with obtaining FDA clearance to commence clinical trials of the cancer stem cell vaccine on a timely basis or at all; the risks associated with adhering to projected preclinical or clinical timelines and the uncertainties of outcomes of development work for product candidates, including those based on destroying cancer stem cells as a potentially safe and effective treatment for various cancers; the risk that future trials of the dendritic cell-based vaccine product candidate, if any, do not confirm the safety and efficacy data generated in the Phase I trial; the need to satisfy performance milestones to maintain the vaccine technology licenses with Cedars-Sinai; the risks associated with obtaining a patent that provides commercially significant protection for each of the cancer vaccine product candidates and the need to obtain licenses from third parties before commercializing the dendritic cell-based vaccine; and the need for substantial additional capital to fund development of product candidates beyond their initial clinical or pre-clinical stages. Additional risks and uncertainties are described in IMUC's most recently filed SEC documents, such as its most recent annual report on Form 10-K, all quarterly reports on Form 10-Q and any current reports on Form 8-K. IMUC undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Source : www.drugs.com

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