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Time to Relapse Significantly Longer With Asenapine in Phase 3 Trial
SAPHRIS was approved by the U.S. Food and Drug Administration (FDA) on August 13 for the acute treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. SAPHRIS can be used as a first-line treatment and is the first psychotropic drug to receive initial approval for both of these indications simultaneously. In Europe, a Marketing Authorization Application (MAA) for asenapine, under the brand name SYCREST(R), is currently under review by the European Medicines Agency (EMEA) for the treatment of schizophrenia and manic episodes associated with bipolar I disorder. The application will follow the Centralized Procedure. These long-term relapse prevention data are included in the European application and will be submitted to FDA in a supplemental application. Schering-Plough has reported additional top-line results for SAPHRIS in long-term clinical studies and additional clinical studies with SAPHRIS are ongoing.
"Schizophrenia is a serious, debilitating disease affecting millions of people worldwide, and there is a need for effective new medications," said Thomas P. Koestler, Ph.D., executive vice president and president, Schering-Plough Research Institute. "These results provide important new data for SAPHRIS and provide physicians insight into the treatment of patients responding to SAPHRIS."
About the Relapse Prevention Study
The Phase III relapse prevention study was a placebo-controlled, double-blind, clinical trial with a randomized withdrawal design that evaluated the long-term efficacy and safety of a sublingually administered investigational dose of SAPHRIS (5 or 10 mg BID) compared to placebo in prolonging time to relapse or impending relapse in patients with stable schizophrenia. A total of 700 patients entered open-label treatment with SAPHRIS for up to 26 weeks. Of these, a total of 386 patients met criteria for stabilization on SAPHRIS and were randomized to treatment in the 26-week double-blind, placebo-controlled phase of the trial.
The primary endpoint of the double-blind phase of the trial - time to relapse or impending relapse - was defined as one of the following: 1) a PANSS (Positive and Negative Syndrome Scale) total score increase of equal to or greater than 20 percent from baseline in the double-blind phase and a CGI-S (Clinical Global Impression-Severity of Illness) score of equal to or greater than 4 at least two days within one week; 2) a PANSS score equal to or greater than 5 on "hostility" or "uncooperativeness" items or on "unusual thought content," "conceptual disorganization" or "hallucinatory behavior" items, and a CGI-S score equal to or greater than 4 (at least two days within one week); or 3) the investigator's judgment of worsening symptoms or increased risk of violence to self (including suicide) or others.
In the double-blind phase of the trial, the incidence of treatment-emergent and treatment-related adverse events was higher with placebo than with SAPHRIS. The most frequently reported adverse events were anxiety (8.2 percent with SAPHRIS vs. 10.9 percent with placebo), increased weight (6.7 percent with SAPHRIS vs. 3.6 percent with placebo) and insomnia (6.2 percent with SAPHRIS vs. 13.5 percent with placebo). Worsening schizophrenia was reported as an adverse event by 4.6 percent of SAPHRIS-treated patients and 16.1 percent of placebo-treated patients; the incidence of adverse events that were also considered a relapse was 7.2 percent with SAPHRIS and 26.6 percent with placebo. The incidence of clinically significant weight gain (equal to or greater than 7 percent increase from baseline) was 3.7 percent with SAPHRIS and 0.5 percent with placebo (mean +/- SD weight change was 0.0+/-4.3 kg and -1.2+/-4.0 kg, respectively). The incidence of markedly abnormal prolactin values (greater than 4 times the upper limit of normal) was 2.8 percent with SAPHRIS and 4.2 percent with placebo.
About SAPHRIS (asenapine)
SAPHRIS is a psychotropic agent approved in the United States for the acute treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. The recommended starting dose of SAPHRIS for the acute treatment of schizophrenia is 5 mg sublingually twice daily. In controlled trials, there was no suggestion of added benefit with a higher dose, but there was a clear increase in certain adverse reactions. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies. While there is no body of evidence available to answer the question of how long a patient with schizophrenia should remain on SAPHRIS, it is generally recommended that responding patients continue beyond the acute response.
Source: Schering-Plough Corporation