Plot twist: FDA pivots on Alkermes' depression drug

On April 2, the FDA served Alkermes a refuse-to-file letter, saying it needed to see data from “additional well-controlled clinical trials” before it would look at an application for its depression drug ALKS 5461. Now, just two weeks later, the agency is changing its tune. 

Dublin-based Alkermes announced Monday that the FDA rescinded the letter and accepted its NDA for review after "productive interactions with the Agency in which Alkermes clarified certain aspects of the NDA submission." The company did not provide the FDA with additional data or analyses and the agency expects to return a decision by Jan. 31, 2019. 

When it received the letter, Alkermes said the FDA “is unable to complete a substantive review” due to “insufficient evidence of overall effectiveness" in the application for ALKS 5461. Alkermes said the FDA requested extra clinical trial data and results from a bioavailability bridging study of ALKS 5461 and reference drug buprenorphine to facilitate its review. The news sent Alkermes' stock tumbling 20%. 

Now, Alkermes says, the FDA's conclusion of "insufficient evidence" came from a misunderstanding: "The basis of that statement did not reflect a complete understanding of the ALKS 5461 NDA submission. And we directed FDA to the relevant information in the NDA," said Alkermes CEO Richard Pops on a conference call Monday. 

But when questioned by analysts, Pops declined to detail what, specifically, the FDA thought was missing from the application. He repeatedly said that ready-to-file letters are usually the result of "facial deficiencies," such as missing information, and emphasized that questions about the quality of the filing will be addressed when the FDA actually reviews the application. 

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“I think it just took a while to get that lens focused the right way for FDA to accept the file,” Pops said on the call. 

While ALKS 5461 is back on schedule, the FDA's about-face is by no means a guarantee of success—the agency has deemed the data complete enough for review, but could still reject it. And it's been a bumpy road for Alkermes. The company finally reported positive data in August 2016, after the drug failed to meet its primary endpoints in two phase 3 trials the previous January. It started a rolling application for ALKS 5461 last August.