Alkermes Reports Phase 3 Study Results for Aripiprazole Lauroxil Published in JCP

Alkermes plc ALKS today announced the publication of results from its phase 3 clinical trial of aripiprazole lauroxil for the treatment of schizophrenia in the Journal of Clinical Psychiatry. Data from the trial showed that multiple dose strengths of aripiprazole lauroxil administered once monthly demonstrated statistically significant reductions in schizophrenia symptoms, compared to placebo. Aripiprazole lauroxil is an investigational, novel, long-acting injectable atypical antipsychotic for the treatment of schizophrenia designed to offer patients an alternative to oral antipsychotic medicines that must be taken daily. Aripiprazole lauroxil was developed based on Alkermes' proprietary LinkeRx® technology and is designed to provide dosing flexibility to address the unique needs of patients with schizophrenia. Once in the body, aripiprazole lauroxil converts to aripiprazole, a molecule that is commercially available under the name ABILIFY®. Results of the study served as the basis for Alkermes' New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) to gain marketing approval of aripiprazole lauroxil for the treatment of schizophrenia, with a regulatory action date of Aug. 22, 2015. "This published study adds to the body of evidence that is influencing the evolution of the treatment landscape for schizophrenia, as more physicians are now recognizing the potential benefits of long-acting injectable antipsychotics and considering their use earlier in disease progression," said study author Henry Nasrallah, M.D., Chair, Department of Neurology and Psychiatry at Saint Louis University School of Medicine. "These statistically significant efficacy data demonstrated aripiprazole lauroxil's ability to provide clinically meaningful symptom control, showing its potential as a new treatment option to help people with schizophrenia." The phase 3, randomized, multicenter, double-blind, placebo-controlled study of aripiprazole lauroxil evaluated 623 patients with schizophrenia. Patients treated once monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) total scores at Week 12, compared to placebo. The improvement from baseline to Week 12 in PANSS total scores was clinically meaningful and statistically significant in both aripiprazole lauroxil dose groups, with a placebo-adjusted mean PANSS score reduction of 10.9 points for the 441 mg dose group (p<0.001) and 11.9 points for the 882 mg dose group (p<0.001). 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. Furthermore, all other secondary endpoints were found to be statistically significant across both doses. Aripiprazole lauroxil was generally well tolerated in the phase 3 study. The most common adverse events in the study were insomnia, akathisia and headache. "Schizophrenia is a serious, chronic disease, and healthcare providers need new, innovative treatment options to address the individual needs of patients," said Elliot Ehrich, M.D., Chief Medical Officer of Alkermes. "Aripiprazole lauroxil is designed to help address the real-world, individual needs of patients and healthcare providers by providing dosing flexibility in a ready-to-use format." Study Design 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 low volume or high 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. About Aripiprazole Lauroxil Aripiprazole lauroxil is an injectable atypical antipsychotic with one-month and extended-duration formulations in development for the treatment of schizophrenia. Once in the body, aripiprazole lauroxil converts to aripiprazole, which is commercially available under the name ABILIFY®. As a long-acting investigational medication based on Alkermes' proprietary LinkeRx® technology, aripiprazole lauroxil is designed to have multiple dosing options and to be administered in a ready-to-use, pre-filled product format.