FDA Rejects Alkermes’ Opioid Modulator Treatment for Depression

man holding gavel and pointing thumbs down

Almost three months to the day after a U.S. Food and Drug Administration (FDA) advisory committee overwhelmingly rejected Alkermes' major depressive disorder (MDD) treatment, ALKS-5461, the company received word that the regulatory agency will not approve the medication.

Late Friday, the FDA issued a Complete Response Letter to Ireland-based Alkermes that informed the company it cannot approve the therapeutics without additional clinical data. The FDA said that data is required in order to “provide substantial evidence of effectiveness of ALKS-5461 for the adjunctive treatment of MDD,” Alkermes said in a brief statement. The company said it plans to meet with the FDA to discuss the CRL and lay out the potential “next steps” for ALKS-5461. Alkermes said the meeting with the FDA will determine whether or not there is a “viable path forward” for its ALKS-5461 program.

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ALKS-5461 was being developed for the treatment of major depressive disorder in patients with an inadequate response to standard antidepressant therapies. An estimated 16.2 million people in the U.S. suffered from MDD in 2016, the majority of whom may not adequately respond to initial antidepressant therapy, Alkermes noted.

The Complete Response Letter caps off a tumultuous year for the depression treatment. In April 2018, the FDA accepted Alkermes' New Drug Application (NDA) for ALKS 5461, only weeks after the regulatory agency 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.” As BioSpace reported last year, 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. But, then in November, the advisory committee voted against the benefit-risk profile of the medication. In overwhelming votes, the committee questioned its efficacy and whether or not it actually provided any real benefit for patients.

With the advisory committee rejection, as well as some of the difficulties Alkermes had during clinical testing, it’s not totally surprising that the FDA rejected ALKS-5461, an oral medicine that acts as an opioid system modulator. Prior to the November rejection by the FDA advisory committee, 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. Alkermes has certainly defended the efficacy of its asset. The company noted in the announcement regarding its rejection that throughout the clinical development program, ALKS 5461 demonstrated a consistent profile of antidepressant activity, safety and tolerability in the adjunctive treatment of MDD.

Shares of Alkermes closed Friday at $33.06. After the company announced the CRL, shares fell about 4.8 percent in after-market trading.

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