Positive results have been reported from a phase 3 study of ALKS 5461 (Alkermes), a once-daily, oral investigational medication for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies. The study met its primary endpoint, showing that treatment with ALKS 5461 significantly reduced symptoms of depression in patients with MDD compared with placebo.
Based on these results, along with other data on the efficacy and safety of ALKS 5461 for the treatment of MDD, Alkermes plans to request a meeting with the FDA’s Division of Psychiatric Products to discuss the filing strategy for the drug, which has received a fast-track designation.
The FORWARD-5 trial was a randomized, double-blind, multicenter, placebo-controlled, sequential parallel comparison design (SPCD) study that evaluated the safety, tolerability, and efficacy of two dose levels of ALKS 5461 (2 mg/2 mg and 1 mg/1 mg) as adjunctive treatment in 407 patients with MDD who had experienced an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI).
The study was conducted in two sequential stages: stage 1 was five weeks in duration; stage 2 was six weeks. In stage 1, the average change from baseline depression scores was calculated for weeks 3 through 5. For stage 2, the average change was calculated for weeks 3 through 6. The results of stages 1 and 2 were then averaged. Depression scores were assessed using the six-item Montgomery–Åsberg Depression Rating Scale (MADRS-6) and MADRS-10. MADRS-6, a subscale of the MADRS-10 assessment tool, focuses on the core symptoms of depression.
In the study, ALKS 5461 2 mg/2 mg met the prespecified primary endpoint of significantly reducing depression scores compared with placebo, as measured by MADRS-6 (P = 0.018). ALKS 5461 2 mg/2 mg also demonstrated statistically significant reductions in MADRS-10 scores compared with placebo (P = 0.026). The 1 mg/1 mg dose of ALKS 5461 showed improvement in depressive symptoms but did not separate significantly from placebo.
The most common adverse events associated with ALKS 5461 included nausea, dizziness, and fatigue.
Source: Alkermes; October 20, 2016.