Ireland-based biopharmaceutical firm Alkermes has reported positive topline results from a randomised, double-blind, placebo-controlled Phase III clinical trial of its new, long-acting injectable antipsychotic agent aripiprazole lauroxil in patients with schizophrenia.
A total of 623 patients treated once-monthly with either 441mg or 882mg of aripiprazole lauroxil showed significant reductions from baseline in positive and negative syndrome scale (PANSS) total scores at week 12, compared with placebo, which was the trial’s prespecified primary endpoint.
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.
The company said that based on the positive results from the Phase III trial, it intends to submit a new drug application (NDA) to the US Food and Drug Administration (FDA) in the third quarter of 2014.
Aripiprazole lauroxil is 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.
Saint Louis University School of Medicine Department of Neurology and Psychiatry chairman Henry Nasrallah said the statistically significant efficacy data show aripiprazole lauroxil’s ability to provide clinically meaningful symptom control in patients struggling with schizophrenia.
"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," Nasrallah said.
"This data comes at a time when the treatment landscape for schizophrenia is evolving; more physicians are now recognising the benefits of long-acting injectable antipsychotics and considering their use earlier in disease progression."
Data from the full analysis set demonstrated significant improvement in PANSS total scores from baseline in both aripiprazole lauroxil dose groups, relative to the placebo treatment group.
The trial has also met the prespecified key secondary endpoint of improvement on the Clinical Global Impression – Improvement scale (CGI-I) versus placebo at week 12.
Alkermes chief executive officer Richard Pops said the company’s 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.
"With this 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," Pops said.
Most common adverse events observed in the Phase III trial were insomnia, akathisia and headache.
The company said that all participants in the double-blind portion of the Phase III trial are eligible to continue in an open-label phase and receive aripiprazole lauroxil for an additional 12 months.
The objective of the trial’s extension phase is to evaluate the safety and long-term durability of effect of once-monthly aripiprazole lauroxil.
Image: Image showing brain areas more active in controls than in schizophrenia patients during a working memory task during a fMRI study. Photo: courtesy of Kim J, Matthews NL, Park S.