On April 2, 2018, Irish biotech Alkermes revealed that it had received a Refusal-to-File letter from the FDA regarding its depression drug ALKS 5461. The announcement caused Alkermes shares to drop 22.4%, and adversely affected the performance of biotech stocks and exchange-traded funds on Monday.[1]

ALKS 5461 is a fixed dose combination of buprenorphine and samidorphan that is used to modulate the opioid system and provide an avenue for treating major depressive disorder in patients with inadequate response to standard therapies.[2] The FDA indicated in its letter that data from “additional well-controlled trials” were needed before it would review Alkermes’ new drug application. The FDA wanted Alkermes to run a bioavailability bridging study to compare ALKS 5461 with buprenorphine. Alkermes had already executed three Phase III clinical trials to test ALKS 5461’s efficacy against treatment-resistant depression. Two of those clinical trials, however, missed their endpoints. Consequently, the FDA was “unable to complete a substantive review” due to “insufficient evidence of overall effectiveness.”[3]

Alkermes disputes the FDA’s conclusions. CEO Richard Pops asserted “[w]e strongly believe that the clinical development program, including data from more than 1,500 patients with [major depressive disorder], provides substantial evidence of ALKS 5461's consistent antidepressant activity and a favorable benefit-risk profile.” Emphasizing the need for new treatment options, Pops stated that Alkermes “[is] extremely disappointed with this decision and the implications for patients in the U.S. suffering from major depressive disorder . . . .” Alkermes has indicated that it will both request a Type A meeting with the FDA and appeal the decision.[4]