Overview of Asenapine Data from Olympia Trial Program Presented at American Psychiatric Association Annual Meeting

Efficacy and safety data support potential of asenapine in the treatment of schizophrenia and bipolar I disorder

WASHINGTON, May 08, 2008 /PRNewswire-FirstCall/ -- Schering-Plough Corporation today announced that an overview of asenapine clinical trials from the Olympia program was presented at the 161st Annual Meeting of the American Psychiatric Association in Washington, D.C., May 3-8. Data from the studies, involving patients with bipolar I disorder and schizophrenia, were presented in two oral presentations (Abstracts # 44 and # 80). Also presented were long-term safety and efficacy data from a clinical trial involving patients with schizophrenia and schizoaffective disorders.

Asenapine, a fast-dissolving, novel psychopharmacologic agent with a unique human receptor signature, was shown to be effective in two short-term bipolar mania studies with a nine-week extension and in two out of four short-term schizophrenia studies. In the third short-term schizophrenia study, neither asenapine nor the active control differentiated from placebo; in the fourth study, asenapine did not differentiate from placebo, while the active control did. Overall, asenapine was well tolerated in the Olympia trial program.

"Despite having effective treatments available, up to 75 percent of schizophrenia patients(1) and many bipolar disorder patients stop taking their medicines because of unwanted side effects or lack of efficacy," said Roger McIntyre, M.D., Associate Professor of Psychiatry and Pharmacology at the and head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto, Canada. "Therefore, new therapies that are both effective and well-tolerated would be welcome additions to the treatment options currently available for improving patient care."

Schering-Plough acquired asenapine in November 2007 through its combination with Organon BioSciences, which developed the investigational antipsychotic agent. The Food and Drug Administration is reviewing a new drug application (NDA) for asenapine in the treatment for schizophrenia and acute manic or mixed episodes associated with bipolar I disorder. The asenapine Olympia clinical trial program thus far has involved over 3,000 patients and has included bipolar mania and acute schizophrenia trials.

"Based on results from the Olympia trial program, we believe asenapine has the potential to address a clinically important unmet need for patients with schizophrenia and bipolar disorder," said Robert J. Spiegel, M.D., Chief Medical Officer and Senior Vice President, Schering-Plough Research Institute.

Olympia Data: Bipolar I Disorder

The bipolar I disorder program includes two placebo- and active-controlled, three-week trials followed by an extension study totaling one year of treatment involving nearly 1,000 patients with bipolar I disorder. Treatment response was measured using the Young Mania Rating Scale (YMRS) score, an 11-item scale used to evaluate manic symptoms.

In the trials, both asenapine and the active-control drug olanzapine* produced greater mean reductions in YMRS total scores versus placebo after three weeks of treatment. Asenapine produced 13- and 14-point reductions in the YMRS total score from baseline to day 21 (P<0.05 versus placebo; olanzapine was also demonstrated to be statistically superior to placebo; there was no direct comparison between asenapine and olanzapine). In a 9-week extension of the 3-week trials, asenapine was found to be noninferior to olanzapine on the primary efficacy measure, change in YMRS.

The overall incidence of treatment-related adverse events (AEs) in the trials was 60.8 percent in the asenapine group, 52.9 percent in the olanzapine group, and 36.2 percent in the placebo group. The most commonly reported adverse events (greater than or equal to 5 percent and twice the rate of placebo) with asenapine included sedation, dizziness, somnolence, oral hypoesthesia (numbness) and weight increase.

Presentation of the overview of the Olympia Program in bipolar I disorder (oral abstract #44) was on Tuesday, May 6, at 12:00 pm in Room 151A.

Olympia Data: Schizophrenia

The schizophrenia program includes four placebo- and active-controlled, six-week trials involving more than 1,300 patients with schizophrenia. In two of the trials involving almost 700 patients, asenapine produced 19- to 20-point reductions in Positive and Negative Syndrome Scale (PANSS) total score and was significantly superior to placebo. PANSS total score is a measure of positive symptoms (e.g., hallucinations and delusions), negative symptoms (such as lack of emotional expression), and general psychopathology symptoms (such as anxiety and depression).

The third study in approximately 260 patients was considered a failed trial as neither asenapine nor the active control olanzapine differentiated from placebo. A fourth trial of approximately 400 patients with acute schizophrenia was considered a negative trial, as the active-control (olanzapine) differentiated from placebo whereas asenapine did not.

The most commonly reported AEs (greater than or equal to 5 percent and twice the rate of placebo) among patients taking asenapine in the short-term schizophrenia trials were somnolence, akathisia (restlessness) and oral hypoesthesia (numbness).

"Schizophrenia is a lifelong illness that requires ongoing treatment to effectively manage the spectrum of symptoms that patients suffer from. As such, new treatments need to demonstrate an acceptable long-term safety profile," said Steven Potkin, M.D., Professor, Department of Psychiatry and Human Behavior, . "We are encouraged that in the long-term trial, asenapine had a lower incidence of clinically significant weight gain (15%) vs olanzapine (36%)."

Presentation of the overview of the Olympia Program in schizophrenia (oral abstract #80) is on Thursday, May 8, at 11:00 am in Room 101.

Long-term Safety and Efficacy Data

In a year long, double-blind, randomized study of 1200 patients with schizophrenia or schizoaffective disorder treated with asenapine or olanzapine (3:1 randomization), the safety evaluation showed that the overall rates of AEs were similar for the asenapine 5-10 mg BID arm and olanzapine 10-20 mg QD arm (drug-related AEs, 60 percent and 61 percent respectively; withdrawal due to serious adverse events, 6.3 percent and 6.8 percent, respectively). On efficacy measures, improvements in PANSS total score were greatest for both asenapine and olanzapine within the first six to eight weeks of treatment and were maintained throughout the 52-week study period. In an exploratory secondary analysis, the between-group difference at 52 weeks favored olanzapine. Most commonly reported AEs (greater than or equal to 10 percent) in both treatment groups were insomnia, worsening psychotic symptoms, weight gain and depression.

Additional Asenapine Data Presentations

Additional asenapine data were presented in poster sessions during the meeting.

About Bipolar Disorder

Bipolar disorder, commonly referred to as manic-depressive disorder, is a chronic, episodic illness characterized by mania (episodes of elevated moods, extreme irritability, and increased energy), depression (overwhelming feelings of sadness, suicidal thoughts), or a combination of both. It affects approximately 1 to 5 percent of adults, including more than 10 million adults in the U.S. and more than four million people in Europe.(2,3,4) The condition can start early in childhood or later in life, with the average age of onset between 15 and 25 years old.(5) Bipolar disorder is the sixth leading cause of disability in the world.(3) About half of the patients with bipolar disorder who recover in response to treatment experience recurrence two years later.(6)

About Schizophrenia

Schizophrenia is a chronic, disabling brain disorder characterized by hallucinations, delusions, and disordered thinking. About 24 million people worldwide (or seven in every 1,000 adults in the population) have schizophrenia,(7) including more than two million people in the U.S.(8) and more than four million people in Europe.(9) People with schizophrenia may hear voices other people don't hear or may believe others are trying to harm them. As a result, they may become socially withdrawn, fearful, and agitated.(8)

About Schering-Plough

Schering-Plough is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription and consumer products as well as to animal health products. Schering-Plough's vision is to "Earn Trust, Every Day" with the doctors, patients, customers and other stakeholders served by its colleagues around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the development of, and potential market for, asenapine. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Part I, Item IA. "Risk Factors" in Schering-Plough's 2008 Q1 10-Q.

    *Olanzapine is marketed as Zyprexa(R) by Eli Lilly


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Posted: May 2008

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