The FDA has turned down Alkermes’ bid to win approval for ALKS 5461 in major depressive disorder. Alkermes said the FDA wants additional clinical data, suggesting a quick fix for the regulatory standoff is unlikely.
ALKS 5461 is a fixed-dose combination of buprenorphine and samidorphan. Alkermes designed the combination to act on the mu- and kappa-opioid receptors and thereby improve outcomes in people who are unresponsive to existing antidepressant therapies. But its clinical development program was dogged by missed primary endpoints and other issues that left scope for doubts about its efficacy.
Those issues have led to a complete response letter. In disclosing the setback, Alkermes said the FDA wants “additional clinical data to provide substantial evidence” of the effectiveness of ALKS 5461. The company will now meet with the FDA to learn whether there is a “viable” path forward for the drug.
Alkermes has another phase 3 trial of ALKS 5461 underway but, according to ClinicalTrials.gov, it is still around 30 months from completion. Two of Alkermes' earlier phase 3 studies lasted roughly 18 months. Depending on exactly what data the FDA requests, Alkermes could be looking at a delay of upward of two years.
The events that led to this point suggest the FDA may want fairly extensive data. The agency issued a refusal to file letter when Alkermes originally submitted its NDA, only to change its mind and accept the submission weeks later.
That proved to be a temporary reprieve for the drug. The FDA fleshed out its concerns with the data package in the materials it prepared for an advisory committee last year. The advisory committee then savaged Alkermes’ filing, taking the company to task for midstudy changes and the influence of a super responder on the outcome of one trial before voting overwhelmingly to reject the drug.
The FDA has followed the committee’s lead, bringing one of the more turbulent reviews of recent times to an end.