Post-Partum Depression

November 20, 2017

Sage Therapeutics announced positive top-line results from two phase III clinical trials with its proprietary i.v. formulation of brexanolone (USAN; formerly SAGE-547) in postpartum depression (PPD). The Hummingbird program included two phase III multicenter, randomized, double-blind, parallel-group, placebo-controlled trials (Study 202B and Study 202C). Trial participants in 202B were required to have a Hamilton Rating Scale for Depression (HAM-D) score of 26 or above prior to treatment. These patients were randomized to one of three treatment groups (brexanolone 90μg/kg/hour, brexanolone 60μg/kg/hour, or placebo) on a 1:1:1 basis. Trial participants in 202C were required to have a HAM-D score of between 20 and 25 prior to treatment. These patients were randomized to one of two treatment groups (brexanolone 90μg/kg/hour or placebo) on a 1:1 basis. Brexanolone achieved the primary endpoint in both trials, a mean reduction from baseline in the HAM-D total score compared to placebo at 60 hours (Study 202B: p=0.0242 for 90µg/kg/h dose and p=0.0011 for 60µg/kg/h dose; Study 202C: p=0.0160 for 90µg/kg/h dose). Patients treated with brexanolone demonstrated mean reductions from baseline in HAM-D total scores of 14 to 20 points at 60 hours maintained to 30 days in both trials. Brexanolone was generally well-tolerated and showed a similar safety profile as seen in earlier studies.

July 18, 2016

Sage Therapeutics released results of a phase II trial of SAGE-547 for the treatment of severe postpartum depression (PPD). The multicenter, placebo-controlled, double-blind, 1:1 randomization trial was designed to enroll up to 32 women. The population studied were women with severe PPD (HAM-D ≥26) who developed severe depression either in the third trimester or within four weeks of childbirth. At baseline, the mean HAM-D scores for both groups was greater than 28. The primary objective of the trial was to evaluate the effect of SAGE-547 on depression as measured by the HAM-D score, compared to placebo, at 60 hours. In addition, patients were monitored during a 30-day follow-up period to assess both safety and efficacy. SAGE-547 achieved the primary endpoint of a significant reduction in the HAM-D score compared to placebo at 60 hours (p=0.008). This represented a greater than 20-point mean reduction in the depression scores of the SAGE-547 group at the primary endpoint of 60 hours through trial completion with a greater than 12-point difference from placebo. The statistically significant difference in treatment effect began at 24 hours, (p=0.006) with an effect that was maintained at similar magnitude through to the 30-day follow-up (p=0.01). Remission from depression, as determined by a HAM-D ≤7, measured at 60 hours, was seen in seven of 10 in the SAGE-547 group compared with one of 11 in the placebo group (p=0.008). Similarly, at 30 days, seven of 10 of the SAGE-547 group and two of 11 in the placebo group were in remission (p=0.03). SAGE-547 was found to be generally well-tolerated with no serious adverse events reported during the treatment and follow-up periods. The company has initiated an expansion program to determine optimal dosing of SAGE-547 in PPD.