Brexanolone IV Granted FDA Priority Review for Postpartum Depression

The solution from Sage Therapeutics may become the first treatment indicated for women with postpartum depression.

The US Food and Drug Administration (FDA) has granted Priority Review for an intravenous medication that is looking to become the first indicated treatment of postpartum depression (PPD).

The New Drug Application (NDA) for brexanolone IV (SAGE-547), an investigative therapy from clinical-stage biopharmaceutical company Sage Therapeutics, has been accepted by the FDA for consideration to treat patients with PPD. As the company’s lead product candidate and a molecular entity being considered for an entirely new mechanism of action, the formulation will be gauged under Priority Review with an action date of December 19, 2018.

Brexanolone IV previously received Breakthrough Therapy Designation from the FDA in September 2016, due to the persistent unmet need in treating women with PPD. It is estimated that 11.5% of all new mothers are identified with PPD in the US annually, with state-by-state ranges varying from 8-20%. The form of depression is the most common medical complication of childbirth to affect women, and often commences between the third trimester of pregnancy or in the months immediately following giving birth.

The NDA for brexanolone IV featured data from a couple of phase 3 multicenter, randomized, double-blind, parallel-group, placebo-controlled US trials under the Hummingbird Program. Its efficacy and safety was evaluated in women with either moderate or severe PPD, aged 18-45 years old. Qualifying women for the study were less than 6 months postpartum at screening and had onset symptoms between their third trimester and the first 4 weeks since giving birth.

In the first study featuring 122 patients with severe PPD, patients were randomized to receive either brexanolone 90 mcg/kg/hour, brexanolone 60 mcg/kg/hour, or placebo. Both treatment groups reported statistically significant mean reductions in Hamilton Rating Scale for Depression (HAM-D) total scores from baseline, with the 90 mcg/kg/hour group reporting a 17.7-point reduction (P = 0.0242) and the 60 mcg/kg/hour group reporting a 19.9-point reduction (P = 0.0011). The placebo group reported just a mean 14-point reduction in HAM-D score.

Researchers noted statistically significant reductions in HAM-D total scores versus placebo at 48 hours following treatment — a rate maintained through the 30-day follow-up in both treatment groups.

In the second study involving 104 patients moderate PPD, patients were randomized 1:1 to either brexanolone 90 mcg/kg/hour or placebo. Patients to receive treatment reported a statistically significant reduction in HAM-D total score of 14.2 points from baseline at 60 hours (P = 0.016), compared to the 12-point mean reduction observed in placebo patients.

Similar to the first study, statistical significance was first observed at 48 hours and remained through Day 7, but not at Day 30. However, the effect observed at 60 hours in the treatment group was maintained through the 30-day follow-up.

In both studies, brexanolone reported good tolerability and similar rates of adverse events across all treatment groups. The most comment adverse events reported included headache, dizziness, and somnolence.

At the time of the studies’ presented results, Jeff Jonas, MD, Sage chief executive officer, expressed satisfaction with the rapid-onset action and duration findings for brexanolone.

“We believe the data represent an unprecedented opportunity in the development of treatments for PPD, and may serve as the catalyst for a paradigm shift in how the disease is approached and, if approved, may change how PPD is treated,” Jonas said.