Preliminary Results for Investigational MDD Tx Announced

The two latest studies failed to meet their primary efficacy endpoint
The two latest studies failed to meet their primary efficacy endpoint

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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