Pill for schizophrenia from Vanda Pharmaceuticals is due out in 2010

Early next year, if all goes according to plan, doctors will be able to prescribe a new antipsychotic drug for patients with schizophrenia. When that happens, investors in a local pharmaceutical firm will surely breathe a sigh of relief.

While it's almost certain that the compound known as Fanapt will reach pharmacy shelves, the drug's future was anything but clear for most of its 13-year existence. Rockville-based Vanda Pharmaceuticals toiled for years on its development, even after larger drugmakers lost interest and the Food and Drug Administration gave the product a thumbs-down.

"Last year at this time, nobody believed in the company, and nobody believed in the compound," said Mihael H. Polymeropoulos, Vanda's president and chief executive. Today, the company has a deal for Fanapt worth nearly half a billion dollars.

Shareholders fled the company in droves last year after a negative ruling from the FDA, and Polymeropoulos says he doesn't blame them. He founded Vanda after earlier careers, mostly in Washington, in the health-care industry. He'd never heard of a case in which the FDA reversed a decision on a drug, but that's what happened after Vanda told the agency that it had misinterpreted some data.

Polymeropoulos says he never wavered in his belief that Fanapt could help people.

"People in my field hold the belief that there are scientific truths to be found, and once you solve the problems they can impact health care," he said. "It is that conviction that allows people to commit themselves for a long period of time despite adversity."

In any case, the chief executive said, it's the prospect of helping schizophrenic patients and not the lure of potential profit that serves as the company's driving force. "My belief is you don't build companies to make money just like a bank," he said. "A health-care company's mission is to develop treatments for people."

Fanapt, like other antipsychotic drugs, controls the way information is carried from one nerve cell to another and reduces the activities of some brain activity associated with schizophrenia. The compound blocks a different combination of neurotransmitters than earlier-generation antipsychotic drugs, Polymeropoulos said. The company says Fanapt targets a more relevant set of neurotransmitter receptors, so that patients are likely to suffer fewer side effects than with other medications.

Polymeropoulos has worked on the drug's development for 10 years, including during his earlier career as head of the Novartis pharmacogenetics unit. The giant drugmaker owned the drug early in its development but sold it when it was streamlining its product pipeline. Polymeropoulos and his start-up acquired the rights.

Today, Novartis is back in the Fanapt business. Under the terms of a deal announced last month, Vanda will receive an upfront payment of $200 million from Novartis for rights to commercialize Fanapt in the United States and Canada. As long as Vanda meets certain development milestones, the company will be eligible for additional payments totaling up to $265 million. Not bad for a company that lost $12.4 million during its second quarter this year, and faced shrinking cash resources of under $30 million.

Fanapt's somewhat arduous path to the marketplace isn't unusual, said Sunil Bhonsle, president of Titan Pharmaceuticals, a company that owned the rights to Fanapt before Novartis and will receive royalty payments for the drug when it goes on sale. It is not uncommon for companies to end up with too many products under development, he said, and for some of those products to go to smaller firms for development.

"There tends to be a pattern where smaller companies do a lot of the innovation, then the larger companies acquire them at a certain point," he said.

Even during a tough economic climate that has most sectors tightening belts, the pharmaceutical industry is on the lookout for potentially lucrative experimental drugs to invest in. Older drug products eventually go off-patent and face new competition from cheaper, generic versions.

According to a recent report by Dealogic Revenue Analytics, the dollar value of acquisitions by pharmaceutical and biotechnology firms is up 23 percent this year. Across all industries, by comparison, that figure is down 35 percent -- at $1.7 trillion, compared with last year's $2.6 trillion.

Vanda is one of the first Washington area firms to benefit from an ongoing global spending spree in this industry, and there are periodic rumors about an acquisition of Rockville-based Human Genome Sciences. As recently as August, HGS's stock jumped 14 percent on speculation that the company's sometime partner GlaxoSmithKline intended to buy the firm. HGS has a potential hit with an experimental drug to treat Lupus.

If other Washington area companies have yet to spark that sort of speculation, it might be because they don't have a product far enough along to tempt buyers, some say.

"In Maryland, our companies are not mature enough yet," said John Holaday, who has started three biotech companies. "We don't have a lot of companies that have products in late-stage trials or products that are already in the marketplace."

Polymeropoulos said his work with Fanapt isn't done yet. The company's next task is to help Novartis launch the drug, in tablet form, to pharmacies starting early next year. After that, he and his firm intend to create a version of the drug that patients will receive as a once-a-month injection.

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New 'Schizophrenia Gene' Prompts Researchers To Test Potential Drug Target

Johns Hopkins scientists report having used a commercially available drug to successfully "rescue" animal brain cells that they had intentionally damaged by manipulating a newly discovered gene that links susceptibility genes for schizophrenia and autism.

The rescue, described as "surprisingly complete" by the researchers, was accomplished with rapamycin, a drug known to act on a protein called mTOR whose role involves the production of other proteins. The idea to test this drug's effectiveness at rescuing impaired nerve cells occurred to the team as a result of having discovered a new gene that appears to act in concert with two previously identified schizophrenia susceptibility genes, one of which is involved in the activation of the protein mTOR. This piecing together of multiple genes adds support for the idea that susceptibility to schizophrenia and autism may have common genetic fingerprints, according to the researchers.

In a report on the work published in the Sept. 24 issue of the journal Neuron, the scientists are careful to say that the genes in question are not the cause of schizophrenia or any other brain/mind disorder in humans. However, these genes do appear to serve as a blueprint for proteins that consistently pop up in a range of mental illnesses in people.

The newfound gene, dubbed KIAA1212, serves as a bridge linking two schizophrenia genes: DISC1 and AKT. Suspecting KIAA1212 as one of many potential binding partners interacting with DISC1, whose name is an acronym for "Disrupted-in-Schizophrenia," the researchers genetically shut down the production of DISC1 proteins in newly born neurons in the hippocampus region of an adult mouse brain. The hippocampus contains a niche where native stem cells give rise to fully developed new neurons. The idea was to deliberately cause these cells to malfunction and then watch what happened.

The scientists found that the newborn neurons were most noticeably defective 14 days after DISC1 suppression and that they were defective in a variety of ways. By manipulating AKT production, or altering KIAA1212, they discovered the very same abnormalities as with DISC1 deficiency, concluding that KIAA1212 is in the same signaling pathway as DISC1 and AKT.

Because mTOR is a well-known downstream effector of AKT, they treated the adult mice harboring those abnormal neurons with rapamycin, a drug known to alleviate the effects of a faulty AKT pathway. It effectively "rescued" the neurons from their defects.

"Our discoveries give us more of the information we need to understand the function of genes associated with psychological diseases," says Guo-li Ming, M.D., Ph.D., an associate professor of neurology and neuroscience in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. "The next step is to create a good animal model that would allow us to test whether candidate drugs will reverse not only the irregularities of brain cells with deficiency of these genes, but also behaviors."

The new neurons with alterations of DISC1, KIAA1212 or AKT in the brains of the Rapamycin-treated mice developed normally, says Hongjun Song, Ph.D., an associate professor of Neurology in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, who collaborated in the research. "What was amazing to us is how potent the drug is, at least on the cellular level," he says. "A number of the neurons' developmental defects -- from enlarged cell size to the misplacement of cell localization and abnormal neuronal processes involved in receiving and sending messages -- were corrected by this one drug."

This study was supported by the National Institutes of Health, the McKnight Foundation, NARSAD, the International Mental Health Research Organization, the Maryland Stem Cell Research Fund, and the March of Dimes.

Authors on the paper, in addition to Ming and Song, are Ju Young Kim, Xin Duan, Cindy Y. Liu, Mi-Hyeon Jang, Junjie U. Guo, Nattapol Pow-anpongkul and Eunchai Kang, all of Johns Hopkins.

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Dainippon schizophrenia drug meets trial goals

Japan's Dainippon Sumitomo Pharma Co Ltd (4506.T) said its experimental schizophrenia drug, lurasidone, was significantly better than placebo in a pivotal late-stage clinical trial, according to data released on Wednesday.

The company said it plans to submit its application seeking U.S. approval to sell the medicine early next year.

Dainippon Sumitomo will decide by autumn whether it will market the new drug, if approved, via its own sales network or a co-promotion deal with another firm or if it will acquire a U.S. company, a spokesman for the mid-sized drugmaker said.

Patients with acute schizophrenia in the 478-subject, six-week, Phase III trial received either 40 milligrams or 120 milligrams of lurasidone daily or a placebo.

Both doses of the drug proved to be statistically significantly better than placebo in the primary goal of the study, which was 30 percent or better improvement in the Positive and Negative Syndrome Scale, the company said.

Fifty-three percent of patients who received 40 mg of lurasidone and 47 percent of those on the 120 mg dose achieved the primary goal compared with 38 percent on placebo.

Both doses of lurasidone were also significantly more effective than placebo on a secondary measure used to test antipsychotic drugs called the Clinical Global Impressions Severity scale, the company said.

In previous trials, lurasidone was also tested at 80 mg and Dainippon Sumitomo said it would submit all three doses for FDA approval.

Lurasidone belongs to a class of drugs known as atypical antipsychotics and works by blocking serotonin receptors in the brain. If approved, it would join an already crowded field of such treatments.

"We're still searching for the right drug for many of these patients. There's no one size fits all," Dr Herbert Meltzer, one of the study's lead investigators and professor of psychiatry at Vanderbilt University School of Medicine, said in a telephone interview.

Patients in the trial had been diagnosed with schizophrenia on average for more than 13 years and most had been previously hospitalized prior to entering the study.

"If you look at the weight gain, the lipid changes, it's among the most benign of any antipsychotic drugs, clearly better than olanzapine, clozapine and Seroquel," Meltzer said.

Olanzapine is the chemical name for Eli Lilly and Co's (LLY.N) widely-used Zyprexa; clozapine in sold by Novartis AG (NOVN.VX) under the brand name Clozaril; and Seroquel is sold by AstraZeneca Plc (AZN.L).

Zyprexa and similar drugs can cause significant weight gain and have been linked to increased risk of diabetes.

But "this class of drugs as a whole is so superior to the first generation drugs," said Meltzer, who plans to present the data from the lurasidone trial at a major medical meeting in December.

Lurasidone was well tolerated with a discontinuation rate nearly identical to placebo -- 40 percent versus 39 percent -- and the adverse events were generally mild, such as restlessness and sleepiness.

"From the point of view of efficacy and side effect profile, once a day administration, the fact that the lower dose works as well as the higher dose, I think this is going to have a very good chance of major acceptance among my colleagues," Meltzer added.

Source : www.reuters.com

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FDA OKs New Schizophrenia, Bipolar Drug

The FDA has approved a new drug called Saphris to treat schizophrenia and bipolar I disorder in adults.

"Mental illnesses like schizophrenia and bipolar disorder can be devastating to patients and families, requiring lifelong treatment and therapy," Thomas Laughren, MD, director of the division of psychiatry products in the FDA's Center for Drug Evaluation and Research, says in a news release.

"Effective medicines can help people with mental illness live more independent lives," Laughren says.

The FDA notes that the most common symptoms of schizophrenia include hearing voices or seeing things that are not there, having false beliefs (for example, believing that others are controlling thoughts, reading minds, or plotting harm), and being inappropriately suspicious or paranoid.

Bipolar I disorder is a chronic, severe, and recurrent psychiatric disorder that causes alternating periods of depression and high, increased activity and restlessness, racing thoughts, fast talking, impulsive behavior, and a decreased need for sleep.

Saphris, which comes in tablets, belongs to a class of drugs called atypical antipsychotics.

The FDA approved Saphris based on clinical trials in which the drug trumped a placebo at reducing schizophrenia symptoms in adults and other trials in which Saphris was better than a placebo at treating symptoms of bipolar disorder.

In clinical trials, the most common side effects reported by schizophrenia patients being treated with Saphris were the inability to sit still or remain motionless, decreased oral sensitivity, and drowsiness.

The most common side effects in clinical trials of patients treated with Saphris for bipolar disorder were drowsiness, dizziness, movement disorders other than the inability to sit still or remain motionless, and weight gain.

All atypical antipsychotic drugs carry a "black box" warning, the FDA's sternest warning, alerting prescribers about an increased risk of death associated with off-label use of these drugs to treat behavioral problems in older people with dementia-related psychosis. Saphris isn't approved for those patients.

Saphris is made by the drug company Schering-Plough.

Source : www.webmd.com

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Earlier death due to new drug

Schizophrenia patients given a cheap older drug are less likely to die prematurely than people on newer treatments, despite the older product's well-known adverse side effects, Finnish researchers said on Monday.

The finding may lead to wider use of clozapine - sold by Novartis as Clozaril, but also available as a generic - instead of newer drugs like AstraZeneca's Seroquel, the current market leader.

Clozapine was the first of a new generation of schizophrenia drugs, known as atypical antipsychotics. But its use has been restricted by health authorities because of safety concerns and patients taking it require regular blood tests.

Despite this, an analysis of 10 years' records for 67,000 patients in Finland found that, compared to treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 per cent.

By contrast, mortality risk was 41 per cent higher for those on Seroquel, known chemically as quetiapine; 34 per cent higher with Johnson & Johnson's Risperdal, or resperidone; and 13 per cent higher with Eli Lilly's Zyprexa, or olanzapine.

'We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment,' study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.

'We should consider whether clozapine should be used as a first-line treatment option.'

Mr Tiihonen estimates clozapine is given to around one fifth of Finnish schizophrenia patients, but less than 5 per cent in the United States.

Clozapine's side effects include agranulocytosis, a potentially fatal decline in white blood cells, and current rules stipulate the drug can only be used after two unsuccessful trials with other antipsychotics.

Mr Tiihonen and colleagues wrote in the Lancet medical journal that these restrictions should be reassessed in the light of their findings, since not using the drug may have caused thousands of premature deaths worldwide.

Seroquel, Zyprexa and Risperdal are among the world's top-selling drugs, with a combined sales of US$12.5 billion (S$18.3 billion) in 2008, although Risperdal now faces generic competition.

Source : www.straitstimes.com

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FDA Considers New Psychiatric Drugs for Children

The U.S. government is considering clearing three blockbuster psychiatric drugs currently taken by adults for use in children and adolescents, the Associated Press reported.

The drugs are now approved to treat schizophrenia and bipolar mania, also known as manic depressive disorder, in adults.

The Food and Drug Administration said the drugs appear to work in adolescents, but reviewers worry about exposing youngsters to the medications' side effects, which include weight gain, high blood pressure and sleepiness.

"These risks are of particular concern because of the lifelong nature of these disorders," Dr. Thomas Laughren, the FDA director for psychiatric products, wrote in documents posted online, the AP reported.

The issues will be discussed at a meeting Tuesday, when outside experts will voice their opinions about the drugs' risks and benefits. The FDA usually follows its advisory panels' advice, the AP said.

The drugs -- made by Pfizer Inc., Eli Lilly & Co. and AstraZeneca -- are currently approved to treat schizophrenia and bipolar mania in adults. Together, they accounted for $7.4 billion in sales last year, according to IMS Health, the AP said.

Many physicians already prescribe these drugs to children and teens. While it is permissible for doctors to prescribe as they see fit, pharmaceutical companies can only promote the drugs for FDA-approved uses, the APadded.

Source : www.empowher.com

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APA: New Drug No Better for Negative Schizophrenia Symptoms

Long-term findings for the novel antipsychotic agent asenapine did not confirm any advantage over second-generation antipsychotics for negative symptoms of schizophrenia.

In a randomized trial, the experimental compound produced the same benefit over 52 weeks as olanzapine (Zyprexa, Zydis) for all measures of both positive and negative symptoms, Nina Schooler, Ph.D., of the State University of New York Downstate Medical Center in New York, and colleagues reported here at the American Psychiatric Association meeting.

Asenapine is one of a new pipeline of antipsychotic agents with lower muscarinic and histaminic receptor affinity, suggesting fewer of the metabolic and other side effects that have plagued second-generation antipsychotics. (See APA: Novel Antipsychotic Promising for Schizophrenia)

The drug is being developed by Schering-Plough for treatment of schizophrenia and bipolar disorder. The company applied for FDA approval on the compound and said it expects a decision before the end of the year.

Earlier in the clinical trials program for asenapine, an unhypothesized benefit turned up -- it appeared to improve negative symptoms of schizophrenia significantly better than risperidone (Risperdal).

These negative symptoms, such as lack of motivation and social withdrawal, are far more likely to persist over time than are the core, positive symptoms of the disorder, "which have a much more waxing and waning form," Dr. Schooler said.

To examine this potential advantage prospectively, the researchers conducted the Aphrodite 25543 study, which included 26 weeks of double-dummy treatment with asenapine (5 to 10 mg bid) or olanzapine (5 to 20 mg qd) in 481 schizophrenia patients who had higher negative than positive symptom scores.

Dr. Schooler's presentation focused on the 26-week extension phase that followed for the 134 asenapine-treated patients and 172 olanzapine-treated patients that remained in the trial.

For the primary outcome of Negative Symptom Assessment Scale 16 scores, there was no significant difference between the drugs at week 52 (P=0.2344).

Likewise, they found no differences -- and little change over time -- for the positive symptom portion of the Positive and Negative Syndrome Scale (PANSS) or for the anxiety and depression portion.

Quality of life also improved similarly for asenapine and olanzapine over the course of the trial (P=0.2838).

Both drugs had a high rate of treatment-emergent adverse events over the total 52-week span of the trial (85.1% for asenapine and 74.1% for olanzapine), although serious treatment-emergent events were less common with the new drug (11.2% versus 4.1%).

The most common adverse events over the entire trial were headache (17.2% versus 11.0%), insomnia (15.7% versus 12.8%), and somnolence (11.9% versus 11.0%), which Dr. Schooler said she didn't believe were dramatically different between drugs.

Weight gain, though, as expected, was substantially higher with olanzapine at 27.9% compared with 6.0% with asenapine (change 4.0 versus ­-1.4 kg, P<0.001).>

Source : www.medpagetoday.com

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FDA Approves New Schizophrenia Drug

Boston (SmartAboutHealth) - The FDA has given approval to a new schizophrenia drug made by Vanda.

The drug is called iloperidone, and was originally denied approval by the agency due to the lack of supporting evidence.

It was approved by the FDA based on evidence of 4 clinical trials that clearly showed that the drug reduced symptoms in patients with schizophrenia more than a placebo.

This is the first drug to ever be approved by the FDA from Vanda, resulting in the company’s shares skyrocketing 7 fold.

Vanda is also in the midst of trials of a drug to treat people who suffer with insomnia.

According to the company, their drug is safer than other leading antipsychotic drugs currently on the market which have been linked to side effects including diabetes and even weight gain.

Leading drugs currently on the market to treat mental disorders include Zyprexa, made by Eli Lilly and Seroquel made by AstraZeneca Plc.

Source : smartabouthealth.net

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