Alkermes now faces a difficult uphill battle to gain regulatory approval for ALKS-5461 as a treatment for MDD.
Shares of Alkermes are down in pre-market trading after two U.S. Food and Drug Administration (FDA) advisory committees gave a thumbs down to the company’s New Drug Application for ALKS 5461, a therapeutic developed for the treatment of depression.
Alkermes announced Thursday that the FDA’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee both voted against the benefit-risk profile of the medication. ALKS 5461, an oral medicine that acts as an opioid system modulator, was being developed for the treatment of major depressive disorder in patients with an inadequate response to standard antidepressant therapies. In a 21-2 tally, the committees voted overwhelmingly against the drug. Additionally, the committees voted 20-3 that the company had not provided substantial evidence that supports the efficacy of ALKS-5461.
Some of the comments from the committee members were blunt, to say the least. Martin Kulldorff, a professor of population medicine and a biostatistician at Harvard Medical School and an FDA committee panelist, said: “I don’t think there’s evidence that this drug works.”
Alkermes Chief Executive Officer Richard Pops said the company was disappointed by the advisory committee vote. He added that the company was also surprised by the “FDA’s characterization of the safety and efficacy data for ALKS 5461.”
ALKs-5461 has had a tumultuous history this year. In April, the FDA accepted Alkermes New Drug Application (NDA) for ALKS 5461, a treatment for major depressive disorder only weeks after the FDA rejected the NDA. The FDA initially refused the NDA for ALKS-5461 due to a lack of “insufficient evidence of overall effectiveness for the proposed indication.” In its Refusal to File letter, the FDA said Alkermes would likely have to initiate additional clinical trials in order to support a resubmission. However, when the FDA did its about-face on the NDA, Alkermes said it did not submit any additional data to the FDA as was initially suggested by the regulatory agency.
The advisors’ rejection of ALKS-5461 was not unexpected. Earlier this week, BioSpace highlighted some of the difficulties the drug has facing approval, including criticism over the methods used to report data from its Phase III FORWARD-5 trial that was used to support the New Drug Application. While that trial was billed as a success, two of its three late-stage clinical trials studying ALKS 5461 in depression failed to meet their primary endpoints.
Pops said Alkermes is “steadfast” in its commitment to making a “meaningful difference” in the lives of people dealing with serious mental health issues, such as major depressive disorder. He added that patients “need and deserve access to novel therapies that work differently than currently available antidepressants.” Pops said Alkermes will continue to work with the FDA as it finalizes its review of the New Drug Application and provides its final verdict on the fate of ALKS-5461. While the two committees overwhelmingly rejected the therapy, the FDA is not bound by that recommendation and could still approve the drug, although that would be a long-shot given the regulatory agency generally sides with the advisory committees. The FDA has set a Prescription Drug User Fee Act target action date for the ALKS-5461 NDA of Jan. 31, 2019.
Trading of Alkermes stock had been halted on Thursday while the committees debated the merits of the NDA, but after the rejection of ALKS-5461, the stock did fall in post- and pre-market trading. The stock is down more than 5 percent in early trading today at$38.50 per share, below Thursday’s close of $40.83.
