The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Alkermes regarding the New Drug Application (NDA) for ALKS 5461, an investigational adjunctive treatment for major depressive disorder (MDD).

ALKS 5461 is an oral medication that acts as an opioid system modulator and is being proposed for once-daily administration. It consists of 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 CRL, the Agency stated that the NDA could not be approved in its current form and that additional clinical data would be needed to substantiate the evidence for the effectiveness of ALKS 5461 as an adjunctive treatment in MDD.

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In November 2018, the FDA’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 21 to 2 that the benefit-risk profile of ALKS 5461 was not adequate to support approval. In the meeting documents, the panel presented a scenario which illustrated their concerns regarding potentially complex drug interactions that may occur in the population for which the drug is intended.

Alkermes plans to meet with the FDA to discuss next steps for ALKS 5461. The novel treatment has been investigated in over 30 clinical trials in more than 1500 MDD patients.

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