Brexanolone (formerly SAGE-547, Sage Therapeutics) helped ease the severity of women’s postpartum depression in two phase 3 clinical trials.
Sage has announced positive top-line results from Study 202B in severe postpartum depression (PPD) and Study 202C in moderate PPD. Its proprietary intravenous formulation of brexanolone achieved the primary endpoint in both trials, a mean reduction from baseline in the Hamilton Rating Scale for Depression (HAM-D) total score compared to placebo at 60 hours. 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 safety profile similar to that seen in earlier studies.
PPD is a common biological complication of childbirth affecting a subset of women typically commencing in the third trimester of pregnancy or within four weeks after giving birth. It is estimated that PPD affects approximately 10% to 20% of women giving birth in the U.S., and up to half of these cases may go undiagnosed without proper screening. There are no approved therapies for PPD and there is a clear unmet medical need for treatment.
“PPD is commonly viewed as a disorder solely experienced by the mother, but it also seriously impacts the child and family members—both immediate and extended,” said Samantha Meltzer-Brody, MD, MPH, associate professor and director of UNC Perinatal Psychiatry Program of the UNC Center for Women’s Mood Disorders and primary investigator of the studies. “In these studies, brexanolone provided a profound and durable effect over the study period that could be an important step in potentially changing the way health care providers think about treating this disorder.”
The two phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials were designed to evaluate the safety and effectiveness of brexanolone in women with moderate and severe PPD. Entry criteria for participants included depressed mood and/or loss of interest and associated symptoms of depression, including appetite problems, sleep problems, motor problems, lack of concentration, loss of energy, poor self-esteem and suicidality that began no earlier than the third trimester and no later than the first four weeks following delivery.
In Study 202B, patients with severe PPD (N = 122) were randomized to one of three treatment groups (brexanolone 90 mcg/kg/hour, brexanolone 60 mcg/kg/hour, or placebo) on a 1:1:1 basis. Brexanolone 90 mcg/kg/hour treatment was associated with a statistically significant mean reduction in HAM-D total score of 17.7 points from baseline compared with a 14.0 point mean reduction in HAM-D total score associated with placebo (P = 0.0242). Brexanolone 60 mcg/kg/hour treatment was associated with a statistically significant mean reduction in HAM-D total score of 19.9 points from baseline compared with a 14.0 point mean reduction in HAM-D total score associated with placebo (P = 0.0011).
Statistically significant differences in the reduction in HAM-D total score of brexanolone versus placebo were first observed at 48 hours and the effect at 60 hours was maintained through the 30-day follow-up with statistical significance for both brexanolone dose groups.
In Study 202C, patients with moderate PPD (N = 104) were randomized to one of two treatment groups (brexanolone 90 mcg/kg/hour or placebo) on a 1:1 basis. Brexanolone treatment was associated with a statistically significant mean reduction in HAM-D total score of 14.2 points from baseline at 60 hours (P = 0.0160) compared with a 12.0 point mean reduction in HAM-D total score associated with placebo.
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 brexanolone group was maintained through the 30-day follow-up.
Brexanolone was generally well tolerated in both studies with similar rates of adverse events across all treatment groups.
Source: Sage Therapeutics; November 9, 2017.