The Food and Drug Administration (FDA)’s Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee voted in favor (17-1) of Zulresso (brexanolone; Sage Therapeutics) Injection for the treatment of postpartum depression (PPD) when administered by qualified staff in a facility that has been certified under a Risk Evaluation and Mitigation Strategies (REMS) program.
The joint recommendation by the Committees was based on safety and efficacy data from 3 placebo-controlled clinical studies. In an analysis of two Phase 3 multicenter, double-blind, randomized, placebo-controlled trials published in The Lancet, treatment with brexanolone led to significant and clinically meaningful reductions in Hamilton Rating Scale for Depression (HAM-D) at the primary timepoint of 60 hours vs placebo. Also, a statistically significant improvement in HAM-D total score was seen within 24 hours of starting treatment and response was durable through the 30-day follow-up.
Brexanolone, an analogue of the endogenous human hormone allopregnanolone, is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors; allosteric modulation allows for varied degrees of desired activity compared with a complete activation or inhibition of the receptor.
According to the meeting documents, the FDA’s major safety concern with brexanolone was the observed loss of consciousness/pre-syncope during the infusion (6 of 140 women exposed to brexanolone). To improve safety, the implementation of a REMS program was recommended.
FDA advisory committees are made up of independent experts who provide recommendations to the Agency regarding potential new treatments. Their decisions are not binding but their recommendations are considered when the FDA reviews NDAs. If approved, Zulresso would be the first drug approved for the treatment of PPD.
For more information visit FDA.gov.