The FDA has told Alkermes it needs to see data from “additional well-controlled clinical trials” before it will review a filing for approval of depression drug ALKS 5461. Alkermes plans to appeal the ruling, but at this stage it looks like the biotech’s attempt to get a mixed set of data past the FDA has failed.
Disclosing news of the FDA’s refusal-to-file letter, Alkermes said the FDA “is unable to complete a substantive review” because the application contains “insufficient evidence of overall effectiveness.”
Remedying that shortcoming could be expensive and time consuming. Full details of what the FDA wants are yet to emerge, but the snippets shared by Alkermes suggest there is no quick fix for the filing. Alkermes said the FDA requested the aforementioned extra clinical trial data and results from a bioavailability bridging study of ALKS 5461 and reference drug buprenorphine to facilitate its review.
The FDA’s take on the data diverges sharply from that presented by management at Alkermes, which has talked up the “comprehensive clinical efficacy and safety package” on ALKS 5461. That package was supposed to be enough to win approval of a drug Alkermes presented as a potential blockbuster. Alkermes’ belief in the drug’s potential is underlined by its commercial preparations, which called for the company to grow its sales force by more than 70% to support ALKS 5461.
That confidence was built on a phase 3 program that experienced more failures than successes. Alkermes put ALKS 5461 through three phase 3 treatment-resistant depression trials. Two of the trials missed their primary endpoints, but Alkermes used the success of the third trial to paint the overall dataset as supportive of the efficacy of ALKS 5461.
The FDA’s refusal to buy into that line of thinking is a blow to people in Alkermes and beyond. Having talked up the strength of the dataset, Alkermes CEO Richard Pops and his colleagues emerge from the setback with dented reputations. More broadly, the FDA’s refusal to even review the data is a blow for any biotech hoping the arrival of Scott Gottlieb, M.D., as commissioner would usher in an era in which the FDA waves through drugs with patchy data packages.
Shares in Alkermes fell 20% in premarket trading.
Analysts at Jefferies said in a note to clients: “Previously, we thought the application would be controversial given it was predicated on single positive PIII trial and two negative PIII studies, and the fact the single positive trial utilized a time-weighted average endpoint (a first for a depression trial) and therefore we felt FDA may require add’l trials.
“Its still unclear what type of a study FDA will require until ALKS meets with FDA in a Type A meeting. Type A meetings address potential disputes btwn the agency and the sponsor and typically occur within 30 days of an RTF letter therefore we may receive some clarity by end of Q2 on next steps forward. An available option to ALKS is data from the ongoing ‘217 trial with ALKS-5461 which could be used to support the NDA application.In mid-2017, the ‘217 trial initiated patient enrollment w/ a target of 325 pts randomized into two arms: ALKS-5461 or placebo. However, it remains to be seen if data from this ongoing trial would be acceptable to FDA given FDA may request a different design. As a result, we have moved our market launch estimate to 2021 from 2019.”