Sunovion announces results from LATUDA open-label study for schizophrenia

Sunovion Pharmaceuticals Inc. today announced results from an open-label study that switched clinically stable, but symptomatic adult outpatients with schizophrenia from other antipsychotic agents to LATUDA (lurasidone HCl) . These data were presented at the 165^th Annual Meeting of the American Psychiatric Association in Philadelphia, Pennsylvania.

This 6-week open-label study included 244 patients who were clinically stable for at least eight weeks prior to the start of the study and had been on stable doses of other antipsychotic agents for at least four weeks. The study's primary endpoint was time to treatment failure (defined as discontinuation due to insufficient clinical response or an adverse event, including exacerbation of underlying disease). In addition, the study was intended to assess the safety and tolerability of switching patients from other antipsychotic agents to LATUDA.

Eligible patients were randomized to one of three LATUDA dosing regimens for the initial two weeks of the study: 1) 40 mg/day for two weeks; 2) 40 mg/day for one week, then an increase to 80 mg/day on Day 8 for Week 2 (uptitration group); and 3) 80 mg/day for two weeks. LATUDA was then flexibly dosed (40-120 mg/day) for the subsequent four weeks of the study across each of the three dosing regimens. The pre-switch antipsychotic agent was tapered by Day 7 to 50% of the original dose and discontinued by the end of Week 2.

The proportion of patients across all LATUDA doses (19/240, 7.9%) that met pre-specified criteria for treatment failure (based on initial randomized dose groups) was as follows:

• LATUDA 40 mg/day: 6.9% (5/72)
• LATUDA 40/80 mg/day (uptitration group): 9.2% (8/87)
• LATUDA 80 mg/day: 7.4% (6/81)

The overall discontinuation rate was 18.9%, with 1.2% of patients discontinuing treatment due to insufficient clinical response and 6.6% due to adverse events.

For patients who were taking concomitant antidepressants, mood stabilizers or antipsychotics at study initiation, approximately half (49.5%) of these patients discontinued use of the concomitant agent by study termination.

Adverse events (at least 5% in all LATUDA doses) observed in this study included nausea, insomnia, akathisia, headache, vomiting, somnolence and dry mouth. Results for all LATUDA-treated patients were as follows:

• Change from baseline at Week 6 LOCF endpoint:
• Weight: -0.7 lbs (n=220)
• Cholesterol: -1.0 mg/dL (n=219)
• Triglycerides: -6.0 mg/dL (n=219)
• Glucose: -1.0 mg/dL (n=219)
• Prolactin: +0.5 (n=219)

Additional data showed that LATUDA-treated patients experienced improvements as assessed by the Positive and Negative Syndrome Scale total (PANSS, -5.8), Clinical Global Impression-Severity scale (CGI-S, -0.3) and the Calgary Depression Scale for Schizophrenia (CDSS, -1.3). These results were based on changes from baseline for LATUDA-treated patients; there was no placebo or other comparator. Results were similar for all three switch strategies.

"An important measure of the acceptability of any antipsychotic agent is how many people are taking it six weeks later," said Joseph McEvoy, M.D., Professor of Psychiatry and Behavioral Sciences at Duke University Medical Center. "The completion rate was notable in this study of LATUDA, with more than 80% of patients making it to six weeks. And when patients did discontinue, only 1% did so due to insufficient clinical response."

"Schizophrenia is a complex disorder whose treatment often requires switching antipsychotic agents," said Antony Loebel, M.D., Executive Vice President and Chief Medical Officer of Sunovion Pharmaceuticals Inc. "We designed this study to help physicians understand how they could switch patients to LATUDA in a real-world setting."

Overall, these findings indicate that switching to LATUDA initiated at therapeutic doses of 40 or 80 mg/day, or uptitrated from 40 mg/day to 80 mg/day, was comparably well-tolerated and effective. In addition, taper and discontinuation of the pre-switch antipsychotic agent over a two-week period was safe and well-tolerated. Since the results of switching to LATUDA were similar for the three initial dose groups, the choice of specific switch strategy may be based on individual need and clinical judgment.

LATUDA received U.S. Food and Drug Administration (FDA) approval for the treatment of schizophrenia on October 28, 2010 and is available in pharmacies across the U.S. and Puerto Rico.