PRINCETON, N.J. and TOKYO -- The U.S. Food and Drug Administration (FDA) has approved Abilify (aripiprazole), a new antipsychotic medication indicated for the treatment of schizophrenia. Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. will jointly market Abilify in the United States. The companies anticipate that the drug will be widely available in pharmacies within two weeks.

Clinical studies involving 1,238 patients with acute relapse of schizophrenia demonstrated that treatment with Abilify provided significant improvements in the positive and negative symptoms of schizophrenia.

Treatment with Abilify was associated with minimal weight change, minimal extrapyramidal symptoms (EPS is a group of involuntary muscle movement disorders) and a modest difference in sedation compared to placebo (11 percent vs. 8 percent). Additionally, the incidence of QTc interval prolongation with Abilify treatment is not different from placebo.

"Abilify represents an important new treatment for schizophrenia," said Jeffrey Lieberman, MD, vice chairman of psychiatry, professor of psychiatry and pharmacology, University of North Carolina at Chapel Hill. "Clinical data show that patients treated with ABILIFY experience significant improvement of their symptoms, and the medication demonstrated an excellent safety and tolerability profile. Given that a large percentage of patients discontinue or switch antipsychotic medication due to inadequate response or side effects, the addition of Abilify to our armamentarium is very exciting."

Schizophrenia affects more than 2 million Americans, and about one percent of the population worldwide. Schizophrenia interferes with a person's ability to think clearly, manage emotions, make decisions and relate to others. This illness tends to manifest itself in early adulthood and is characterized by positive symptoms, such as hallucinations, delusions, and paranoia, as well as negative symptoms, such as social withdrawal and emotional flatness. While there is no cure for schizophrenia, it is a treatable illness.

"This approval will enable Bristol-Myers Squibb to further realize its mission of extending and enhancing human life in important new ways," said Peter R. Dolan, chairman and CEO. "For patients and their caregivers, as well as for physicians, Abilify represents new hope for thousands of people with schizophrenia. For Bristol-Myers Squibb, it marks the beginning of a promising new era for our company when we will be providing a new generation of innovative medicines for the benefit of patients everywhere. And I am pleased that we have Otsuka at our side as we begin this great journey."

The efficacy of Abilify in the treatment of schizophrenia was evaluated in short-term (4- and 6-week), placebo-controlled trials of acutely relapsed patients. The primary measures used to assess symptoms of schizophrenia were the Positive and Negative Syndrome Scale (PANSS); the PANSS positive subscale, which rates seven positive symptoms of schizophrenia; the PANSS negative subscale, which rates seven negative symptoms of schizophrenia; and the Clinical Global Impression (CGI) scale, which allows physicians to assess the overall clinical state of the patient. In three studies involving 1,238 patients, ABILIFY was statistically superior to placebo in improving the symptoms of schizophrenia as evaluated by PANSS total score, PANSS positive score, PANSS negative score and CGI-severity score.

The incidence of reports of EPS as an adverse event in the short-term, placebo-controlled trials with ABILIFY was 6 percent compared to 6 percent for placebo. Abilify demonstrated a favorable weight profile in short-term clinical trials. In these studies, there was a slight difference in mean weight change between Abilify and placebo patients (0.7 kg versus -0.05 kg, respectively).

The safety and tolerability of Abilify has been established in studies involving more than 5,500 patients with approximately 3,600 patient-years of exposure, including more than 1,250 patients who were treated for at least one year. In short-term (4- and 6-week) placebo-controlled trials, there was no difference in the incidence of discontinuation due to adverse events between patients treated with Abilify (7 percent) and placebo (9 percent). The most commonly reported adverse events with an incidence of greater than 15 percent and greater than placebo in short-term clinical trials with Abilify were headache (32 percent versus 25 percent for placebo), anxiety (25 percent versus 24 percent for placebo) and insomnia (24 percent versus 19 percent for placebo).

As with other drugs having efficacy in schizophrenia, the mechanism of action of Abilify is unknown. However, it has been hypothesized that Abilify works differently than other antipsychotics. Specifically, it is proposed that the efficacy of Abilify is mediated through a combination of partial agonist activity at dopamine D2 receptors and serotonin 5HT1A receptors, and antagonist activity at serotonin 5HT2A receptors. Partial agonism refers to the ability to both block a receptor if it is overstimulated and to stimulate a receptor when activity is needed.

Abilify is administered as a once-daily oral tablet. The effective dose range is 10 to 30 mg. The recommended starting and target dose of 10 or 15 mg daily enables physicians to initiate therapy at an effective dose without the need to titrate. Dosage can be subsequently adjusted to optimize individual patient response. Tablets may be administered at any time of the day, with or without food. Abilify is available in 10 mg, 15 mg, 20 mg and 30 mg tablets.

Source: PRNewswire