Alkermes plc (NASDAQ: ALKS) today announced the presentation of data from its phase 3 clinical trial of aripiprazole lauroxil, an investigational drug candidate in development for schizophrenia, at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting in Hollywood, Fla. In the pivotal study, both doses of aripiprazole lauroxil tested, 441 mg and 882 mg administered once-monthly, met the primary endpoint with statistically and clinically significant reductions in Positive and Negative Syndrome Scale (PANSS) scores, met all secondary endpoints and demonstrated significant improvements in schizophrenia symptoms versus placebo. This is the first demonstration of the efficacy of a range of doses of a long-acting injectable form of aripiprazole in a randomized clinical trial. The company remains on track to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the third quarter of 2014.
"With these compelling phase 3 data in hand, we are moving forward expeditiously to bring aripiprazole lauroxil to patients with schizophrenia and their families," said Serge Stankovic, M.D., MSPH, Senior Vice President, Clinical Development and Medical Affairs of Alkermes. "With a deep background in the development of long-acting injectable antipsychotic medicines, our scientists designed aripiprazole lauroxil rationally, in a ready-to-use format with multiple dosing options, to meet the individual needs of patients and the physicians and nurses who treat them."
Data from the full analysis set of the phase 3 study showed:
- During the 12-week, double-blind treatment period, patients treated once-monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically and clinically significant placebo-adjusted mean reductions from baseline in PANSS total scores (-10.9 points, p<0.001 for aripiprazole lauroxil 441 mg; and -11.9 points, p<0.001 for aripiprazole lauroxil 882 mg).
- In addition to meeting the prespecified primary efficacy endpoint of PANSS total score reduction, the study also met the prespecified key secondary endpoint of improvement on the Clinical Global Impression - Improvement (CGI-I) scale for each aripiprazole lauroxil group versus placebo at Week 12 (p<0.001). Both of the aripiprazole lauroxil dosing groups demonstrated significant improvement at all post-baseline visits.
- Additionally, all other secondary endpoints were found to be statistically significant across both doses.
- Overall, 64% of patients who received aripiprazole lauroxil completed the study, compared to 46% of patients who received placebo.
- Aripiprazole lauroxil was generally well tolerated in the study, and the observed safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache.
The phase 3, randomized, multicenter, double-blind, placebo-controlled study was designed to assess the efficacy, safety and tolerability of aripiprazole lauroxil in patients experiencing acute exacerbation of schizophrenia. The trial included adult patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®) criteria for schizophrenia and had a PANSS total score of 70 or higher at study baseline.
A total of 623 patients were randomized to receive once-monthly intramuscular injections of aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg or a matching placebo injection of either high volume or low volume for 12 weeks. Following randomization, patients received their first injection along with daily oral study drug for the first three weeks. Patients randomized to the two aripiprazole lauroxil treatment groups received oral aripiprazole for those initial three weeks, while patients randomized to the placebo group received matching oral placebo for three weeks. A total of 596 patients were included in the full analysis set, as defined by those who received at least one dose of study drug and had at least one primary efficacy assessment following administration of study drug.
The primary efficacy endpoint of the study was the mean change from baseline at Week 12 in PANSS total score, using an analysis of covariance (ANCOVA) with a last observation carried forward (LOCF) approach. The Hommel procedure was used for multiple hypothesis testing. Efficacy was also analyzed using a mixed model for repeated measures (MMRM) as a sensitivity analysis.
All participants in the double-blind portion of the study were eligible to continue in an open-label phase and receive aripiprazole lauroxil for an additional 12 months. The objective of the extension phase of the study is to assess the safety and long-term durability of effect of once-monthly aripiprazole lauroxil.