Alkermes' ALKS 5461 Receives FDA Refusal to File Letter for Treatment of MDD

The US Food and Drug Administration (FDA) issued a Refusal to File letter regarding its new drug application (NDA) for ALKS 5461 for adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies.

The once-daily, oral investigational medicine was unable to complete a substantive review of the regulatory package based on insufficient evidence of overall effectiveness for the proposed indication upon its preliminary review.

Additional well-controlled clinical trials are needed prior to the resubmission of the NDA or the treatment. The FDA requested the conduct of a bioavailability study to generate additional bridging data between the treatment and reference listed drug, buprenorphine.

“We are extremely disappointed with this decision and the implications for patients in the US suffering from major depressive disorder, a serious disease where there is a clear and urgent need for new treatment options for patients and their families,” Richard Pops, chief executive officer, Alkermes, said in a statement. “We strongly believe that the clinical development program, including data from more than 1500 patients with MDD, provides substantial evidence of ALKS 5461’s consistent antidepressant activity and a favorable benefit-risk profile.”

Alkermes, disagreeing with the FDA’s decision, plans to appeal, and will seek immediate guidance including requesting a Type A meeting with the FDA to determine next steps and the additional information needed to resubmit the NDA.

ALKS 5461, a proprietary, investigational medicine with a novel mechanism of action for the adjunctive treatment of MDD, acts as an opioid system modulator. It’s a fixed-dose combination of buprenorphine, a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, and samidorphan, a mu-opioid receptor antagonist.

In the US, an estimated 16.2 million people suffered from MDD in 2016 with a majority not adequately responding to initial antidepressant therapy.