Alkermes plc (NASDAQ: ALKS) today announced positive topline results from a randomized, double-blind, placebo-controlled phase 3 clinical trial of aripiprazole lauroxil in 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 (p<0.001 aripiprazole lauroxil 441 mg, p<0.001 aripiprazole lauroxil 882 mg), which was the prespecified primary endpoint in the study. Based on the positive results from this phase 3 study, Alkermes plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the third quarter of 2014. Aripiprazole lauroxil is a new, long-acting injectable antipsychotic agent designed to provide patients with once-monthly dosing of a medication that, once in the body, converts to aripiprazole, a molecule that is commercially available under the name ABILIFY®.
"These statistically significant efficacy data demonstrate aripiprazole lauroxil's ability to provide clinically meaningful symptom control in patients struggling with schizophrenia," said Henry Nasrallah, M.D., Chair, Department of Neurology and Psychiatry at Saint Louis University School of Medicine. "A once-monthly version of aripiprazole with multiple dose strengths would be a welcome addition since it would enhance current treatment options and provide dosing flexibility. These data come at a time when the treatment landscape for schizophrenia is evolving; more physicians are now recognizing the benefits of long-acting injectable antipsychotics and considering their use earlier in disease progression."
Data from the full analysis set showed statistically significant improvement in PANSS total scores from baseline in both aripiprazole lauroxil dose groups, relative to the placebo treatment group. In addition to meeting the prespecified primary efficacy endpoint, the study also met the prespecified key secondary endpoint of improvement on the Clinical Global Impression - Improvement scale (CGI-I) versus placebo at week 12 (p<0.001).
"Our goal has been to develop a differentiated long-acting injectable product candidate responsive to the real-world needs of patients and healthcare providers, providing the proven efficacy of aripiprazole administered once-monthly in a ready-to-use format with multiple dosage strengths," stated Richard Pops, Chief Executive Officer of Alkermes. "With these positive data in hand, we will complete the preparation of our NDA, which we plan to submit next quarter, and continue our preparations to bring this important new medicine to patients and healthcare providers."
Aripiprazole lauroxil was generally well tolerated in the phase 3 study, and the 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.
Alkermes will present comprehensive data from the phase 3 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal.
Phase 3 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 placebo 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. The primary efficacy endpoint of the study was the change from baseline at week 12 in PANSS total score, using an analysis of covariance (ANCOVA) with a last observation carried forward (LOCF). The key secondary endpoint was the CGI-I score at week 12.
All participants in the double-blind portion of the study are 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.
Alkermes will host a conference call today, April 8, 2014, at 8:00 a.m. EDT (1:00 p.m. BST), to discuss these topline results. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988. The conference call will also be webcast on the Investors section of Alkermes' website at www.alkermes.com. In addition, a replay of the conference call will be available from 10:30 a.m. EDT (3:30 p.m. BST) on Tuesday, April 8, 2014, through 5:00 p.m. EDT (10:00 p.m. BST) on Tuesday, April 15, 2014, and may be accessed by visiting Alkermes' website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.