FDA panel slams Alkermes’ opioid-based depression drug

It has been a long and difficult road for Alkermes’ new depression drug, and Thursday’s advisory committee vote won’t make it any easier. The panel voted 21-2 against recommending the drug for approval, teeing it up for a likely rejection come January. 

Alkermes is seeking the FDA nod for the drug, ALKS-5461, as a treatment for major depressive disorder, the most common form of depression. The panel included both the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Committee because ALKS-5461 contains an opioid: buprenorphine. 

The panel also voted 20-3 that Alkermes did not provide "substantial evidence" to support the efficacy of ALKS-5461, a combination of buprenorphine and samidorphan, a new molecular entity designed to ward off buprenorphine’s negative effects, such as addiction. The only positive vote was the safety one, and even then, ALKS-5461 barely squeaked through—the panel voted 13-10 that Alkermes had "adequately characterized the safety profile of buprenorphine/samidorphan for the adjunctive treatment of major depressive disorder." 

ALKS-5461 works differently from currently available depression drugs, offering hope in a field that has lacked investment and innovation. If approved, it could become an option for people who don’t respond to traditional antidepressants. 

RELATED: FDA staff spotlight big—but expected—issues on Alkermes' depression drug

Felipe Jain, M.D., an assistant clinical professor of psychology at the University of California, San Francisco, voted no "as somebody who prescribes opiates to patients with treatment-resistant depression." 

"I did not feel the evidence was convincing of substantial effectiveness," he said. 

There were "too many methodological issues," said another panelist, Satish Iyengar, Ph.D., a professor of statistics at the University of Pittsburgh. 

RELATED: Plot twist: FDA pivots on Alkermes' depression drug

While the FDA is not obligated to heed an advisory committee’s advice, it tends to stick to the recommendation. The agency is expected to make a decision on ALKS-5461 by Jan. 31. 

"A combination of poor choice in statistical methods and an unsupported change in clinical endpoints drove the vote. The outcome leads to a high likelihood of issuance of a CRL. We currently still model $250M in peak sales, and we await FDA clarity on requirements for '5461 and whether the ongoing PIIIb would be sufficient," Jefferies analysts wrote in a note Thursday evening.

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