Analysis of three studies of Zulresso (brexanolone injection) in postpartum depression published in the Lancet.- Sage Therapeutics.

Sage Therapeutics announced The Lancet has published an integrated analysis across three, double-blind, randomized, placebo-controlled studies of Zulresso (brexanolone injection) in women with postpartum depression (PPD). This new analysis, published for the first time, demonstrated significant and clinically meaningful reductions in HAM-D total score, a common measure of depression severity, following treatment with brexanolone 90 �g/kg/h at the primary timepoint of 60 hours compared with placebo. Statistically significant improvement in the HAM-D total score was first observed within 24 hours of initiating treatment and treatment response was durable through the 30-day follow-up. The most common adverse events during treatment across all studies were headache, dizziness and somnolence. The FDA has conditionally accepted the proprietary name Zulresso for Sage�s intravenous formulation of brexanolone.

An analysis of the integrated comparative efficacy of brexanolone injection 90 �g/kg/hr [BRX90] versus placebo groups across two Phase III studies (studies 1 & 2) and one Phase II study completed in 2017 was conducted; as a unique dose group, brexanolone injection 60 �g/kg/hr [BRX60] in study 2 was not included in the integrated efficacy analysis but was included in integrated analyses of safety. Mean pre-dose HAM-D total scores for the integrated BRX90 arms and placebo arms were 25.5 and 25.7, respectively. At the 60-hour primary timepoint, there were significantly larger mean reductions from baseline in HAM-D total scores with BRX90 relative to placebo (-17.0 vs. -12.8). These treatment differences at Hour 60 were maintained at Day 30. Brexanolone injection showed similar results in subjects with and without a concomitant antidepressant use, with both subgroups demonstrating significant differences in change from baseline HAM-D total score versus placebo at Hour 60. Additionally, brexanolone injection had higher rates of remission (defined as HAM-D total score less or equal to 7; BRX90, 50.0%; placebo, 26.4%) and response (defined as at least 50% reduction in HAM-D total score; BRX90, 74.5%; placebo, 5.7%) than placebo at Hour 60.

Across all brexanolone injection subjects, including subjects who received BRX60, there were two (1%) brexanolone subjects with at least one serious adverse event (vs. no placebo subjects), and there were three (2%) brexanolone subjects with at least one severe adverse event compared with two (2%) placebo subjects. There were no deaths.