Alkermes announced preliminary topline results from two Phase 3 trials, FORWARD-3 and FORWARD-4, for ALKS 5461, for the adjunctive treatment of major depressive disorder (MDD) in patients who have inadequate response to standard therapies. 

FORWARD-3 and FORWARD-4, the first two of three Phase 3 efficacy studies from the comprehensive FORWARD (Focused On Results With A Rethinking of Depression) pivotal program, are randomized, double-blind, multicenter, placebo-controlled trials. They evaluated the efficacy, safety, and tolerability of ALKS 5461 as adjunctive treatment of MDD in patients who had an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). The prespecified primary efficacy endpoint of both studies was the change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) scores.

RELATED: Positive Safety, Tolerability Data for ALKS 5461 in MDD Study

FORWARD-4 enrolled 385 patients to evaluate two dose levels of ALKS 5461 (2mg/2mg, 0.5mg/0.5mg) compared to placebo. A trend toward efficacy was seen with the 2mg/2mg dose on the primary endpoint, with the entire 2mg/2mg dose group achieving statistical significance on the MADRS endpoint, in the post hoc analyses. FORWARD-3 enrolled 429 patients to evaluate the 2mg/2mg dose of ALKS 5461 vs. placebo. Results showed that placebo response was greater than that observed in FORWARD-4 and no treatment effect of ALKS 5461 was observed. Both studies failed to meet the primary efficacy endpoint.

Alkermes’ third efficacy study, FORWARD-5, is ongoing, evaluating two dose levels of ALKS 5461 (2mg/2mg and 1mg/1mg) for the adjunctive treatment of MDD. The Company intends to provide an update on the study later this quarter.

ALKS 5461, a combination of samidorphan and buprenorphine, is a proprietary, once-daily, oral, investigational medication with a novel mechanism of action for MDD treatment. It acts as a balanced neuromodulator in the brain to rebalance brain function that is dysregulated when in the state of depression.

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