Data from the trials will support Sage Therapeutics’ new drug application, to be submitted to the FDA in 2018.
Massachusetts-based Sage Therapeutics has announced positive top-line results from 2 phase 3 trials of brexanolone, an intravenous formulation for the treatment of severe and moderate postpartum depression (PPD).
Brexanolone is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors. The drug has been granted Breakthrough Therapy designation by the US Food and Drug Administration (FDA) and PRIority Medicines (PRIME) designation from the European Medicines Agency (EMA) in PPD.
Sage Therapeutics plans to file a New Drug Application (NDA) with the FDA in 2018.
In Study 202B in severe PPD and Study 202C in moderate PPD, brexanolone achieved the primary endpoint — a mean reduction from the baseline in the Hamilton Rating scale for Depression (HAM-D) total score compared to placebo at 60 hours (Study 202B: p=0.0242 for 90 µg/kg/h dose and p=0.0011 for 60 µg/kg/h dose; Study 202C: p=0.0160 for 90 µg/kg/h dose).
Brexanolone-treated patients experienced mean reductions from baseline in HAM-D total scores of 14 to 20 points at 60 hours, maintained to 30 days in both trials. The drug was generally well tolerated, and exhibited a similar safety profile to earlier studies, according to a Sage statement.
“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,” 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 phase 3 studies. “These data meaningfully advance our understanding of PPD and may prompt medical professionals to evaluate how PPD is perceived, identified and treated within their practices in the future.”
The 2 studies were part of the Hummingbird Phase 3 program — 2 phase 3, multicenter, randomized, double-blind, parallel-group, placebo controlled trials 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.
Patients enrolled in both trials were required to have had a Major Depressive Episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, and to also be <6mos postpartum at time of enrollment.
Participants in 202B were required to have a HAM-D score of 26 or above prior to treatment. These patients were randomized to one of three treatment groups (brexanolone 90 μg/kg/hour, brexanaolone 60 μg/kg/hour, or placebo) on a 1:1:1 basis.
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