Alkermes Initiates NDA Rolling Submission of ALKS 5461 for MDD

Alkermes plc has initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of ALKS 5461 for the adjunctive treatment of major depressive disorder (MDD).

The company expects to complete the submission of the NDA by the end of 2017.

The drug has been granted FDA Fast Track designation, which is intended to facilitate the development and expedite the review of medicines planned to treat serious conditions and address unmet medical needs, and allows for the submission of completed portions of the NDA on a rolling basis, including eligibility for priority review.

“The initiation of the rolling submission for ALKS 5461 is an important first step in the registration process for ALKS 5461, as we work to bring this potential new medicine to patients suffering from major depressive disorder. ALKS 5461 represents a novel mechanism of action for the treatment of MDD, a condition for which millions of patients in the United States do not achieve an adequate response to standard antidepressant therapies,” stated Elliot Ehrich, M.D., executive vice president, research and development, Alkermes. “We expect to complete the submission of the NDA by year-end 2017 and will continue to collaborate closely with the FDA as we work expeditiously toward making ALKS 5461 available to patients and their healthcare providers.”

The rolling submission decision follows a pre-NDA interaction with the FDA that set the company up to file more than 30 clinical trials — including the positive FORWARD-5 trial and 2 earlier studies that failed to hit the mark because of what the company said was a high-placebo response. During the interaction, Alkermes and the FDA agreed upon the proposed content and timing of the ALKS 5461 NDA submission.

In June, Alkermes announced the initiation of study 217, a phase 3b trial, to evaluate the efficacy and safety of ALKS 5461 in patients suffering from MDD who have an inadequate response to commonly prescribed drugs for depression including selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). In addition to the traditional Montgomery-Asberg Depression Rating Scale (MADRS) assessment for improvement of depression symptoms, the study will include other scales to further evaluate the drug’s potential benefits on mood and associated behavioral domains regulated by endogenous opioid modulation.

The 11-week, 2-stage study will randomize 325 patients, incorporating design features informed by the FORWARD pivotal program helping to ensure rigorous patient selection, monitoring and evaluation. The primary objective is to assess the drug’s ability to improve depressive symptoms measured by MADRS-6 and MADRS-10. Specific scales added to evaluate additional potential benefits include the Connor-Davidson Resilience Scale (CD-RISC), Snaith-Hamilton Pleasure Scale (SHAPS), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, Brief Pain Inventory-Short Form (BPI-SF) and the Clinical Global Impression Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales.

ALKS 5461, a proprietary, once-daily oral medicine, acts as a balanced neuromodulator in the brain and represents a novel mechanism of action for the adjunctive treatment of MDD. Consisting of samidorphan and buprenorphine, it’s designed to rebalance brain function dysregulated in the state of depression.

If approved, the drug could open a new line of treatment for patients — estimated to be in the millions worldwide — who struggle to control symptoms of major depressive disorder despite drug therapy.

A press release was made available.

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