Early results of Phase III trials of LKS 5461 (samidorphan + olanzapine) in depression fail to meet endpoints- Alkermes

Alkermes announced preliminary topline results from FORWARD-3 and FORWARD-4, the first two of three phase III efficacy studies to read out from the comprehensive FORWARD pivotal program* for ALKS 5461 (samidorphan + olanzapine) for the adjunctive treatment of major depressive disorder (MDD) in patients who have an inadequate response to standard therapies for clinical depression. Neither of the two studies met the prespecified primary efficacy endpoint, which compared ALKS 5461 to placebo on the change from baseline on the Montgomery–Åsberg Depression Rating Scale (MADRS).

FORWARD-5, the third pivotal efficacy study in the FORWARD program, is ongoing, testing two dose levels of ALKS 5461 (2mg/2mg and 1mg/1mg). FORWARD-5 shares common design and analysis features with FORWARD-4. Based on information gained from FORWARD-3 and FORWARD-4, patient enrollment in FORWARD-5 will be increased and the statistical analysis plan will be updated. Alkermes will provide an update later this quarter on the projected timing of completion of FORWARD-5. In the case of a clear positive outcome for FORWARD-5, Alkermes believes that the evidence provided by it and the previously completed successful, randomized, placebo-controlled phase II study, together with supportive evidence from FORWARD-4, collectively could provide substantial evidence of efficacy for ALKS 5461 for the adjunctive treatment of MDD. In that case, Alkermes would request a meeting with the U.S. Food and Drug Administration’s (FDA) Division of Psychiatric Products to discuss the regulatory path for this Fast Track designated medicine.


* FORWARD-1, FORWARD-2, FORWARD-3, FORWARD-4, FORWARD-5.