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NDA submitted for Abilify for treatment of acute bipolar mania

PRINCETON, N.J., and TOKYO, JAPAN, July 16, 2003 -- Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd. announced that a Supplemental New Drug Application (sNDA) for Abilify(aripiprazole) for the treatment of acute mania in patients with bipolar disorder has been submitted to the FDA, which approved Abilify for the treatment of schizophrenia in November 2002.

The sNDA filing is based on efficacy and safety data from three 3-week placebo-controlled studies and a 12-week active-controlled study in the treatment of acute mania. The four trials examined the efficacy and safety of Abilify at doses of 15-30 mg daily using the Young Mania Rating Scale (Y-MRS) as the primary assessment tool.

Data from two of the three placebo-controlled studies showed Abilify to be superior to placebo in symptom improvement. In these two pivotal trials, improvement with Abilify as measured by the Y-MRS was statistically superior to placebo by Day 4. In the third trial, Abilify demonstrated symptom improvement comparable to that of the other studies; however, due to a high placebo response rate (approximately 40%), Abilify did not show statistical separation from placebo.

In the active-controlled study, Abilify demonstrated comparable symptom improvement (as measured by improvement in Y-MRS score) and a significantly higher response rate compared to that of haloperidol (50% vs. 28%; p<0.001). Response was defined as a greater than or equal to 50% decrease in scores on the Y-MRS while remaining on therapy.

"The data in this sNDA submission examined Abilify in the treatment of acute mania," said Joseph R. Calabrese, M.D., Professor of Psychiatry, Case Western Reserve University School of Medicine, and Director, Mood Disorders Program, University Hospitals of Cleveland. "Abilify is an important therapeutic option for the treatment of schizophrenia, given its proven efficacy, safety and tolerability profile. Evaluating the use of Abilify in patients with acute mania is also critical, because additional treatment options for this illness are needed."

Safety data from more than 1,141 patients enrolled in short and long-term bipolar mania clinical trials was also included in the sNDA submission. In the placebo-controlled bipolar trials, the incidence of clinically significant weight gain, defined as >7% increase in body weight from baseline, was low among both patients treated with Abilify (2.9%) and those receiving placebo (2.4%). Somnolence was reported by 14% of patients treated with Abilify and 8% of patients receiving placebo.

In the placebo-controlled trials, discontinuations due to adverse events with Abilify were similar to that of placebo (11% vs. 10%, respectively). The discontinuation rate for adverse events with Abilify in the active-controlled study was markedly lower than that of haloperidol (18% vs. 49%, respectively). Common adverse events in the placebo-controlled studies (occurring at a rate of greater than 5% and twice that of placebo) included akathisia, accidental injury and extrapyramidal syndrome (EPS). These adverse events were generally mild to moderate in severity and infrequently led to treatment discontinuation. Akathisia describes a sustained, subjective sense of restlessness, and EPS describes a range of muscular side effects, including tremors, muscle rigidity and abnormal and involuntary muscle movements.

Abilify, the most recently approved treatment for schizophrenia in the United States, Mexico, Brazil, Puerto Rico, Peru, and Australia, has been prescribed for more than 150,000 people in the United States. Abilify is available in 10 mg, 15 mg, 20 mg, and 30 mg tablets. When starting treatment, some patients experience side effects such as headache, anxiety, insomnia, nausea, vomiting, sleepiness, lightheadedness, restlessness, and constipation.

In short-term (4- and 6-week) placebo-controlled schizophrenia trials, there was no statistical difference in the incidence of discontinuation due to adverse events between patients treated with Abilify and placebo (7% and 9%, respectively) or incidence of EPS (6% vs. 6%). In addition, studies showed that Abilify was associated with a moderate difference in sedation compared to placebo (11% vs. 8%, respectively), and did not cause significant QT(c) interval changes. Bristol-Myers Squibb and Otsuka submitted a sNDA for the long-term treatment of schizophrenia in February 2003.

Abilify is available by prescription only. Patients should talk to their physician for more information. Full prescribing information is available at

Source: Bristol-Myers Squibb; Otsuka Pharmaceutical Co.

Posted: July 2003