Phase 3 data support brexanolone for postpartum depression
NEW YORK — Results from two studies presented here demonstrated the effectiveness of brexanolone for severe and moderate postpartum depression.
“Postpartum depression, or PPD, is a serious mood disorder that is the most common medical complication of childbirth, typically beginning in the third trimester of pregnancy or within 4 weeks after giving birth,” Samantha Meltzer-Brody, MD, MPH, of department of psychiatry at the University of North Carolina School of Medicine, told Healio Psychiatry.
“It is estimated that PPD affects more than 400,000 mothers in the U.S. each year, and without proper screening, up to half of all cases may go undiagnosed,” she continued. “PPD may have devastating consequences for a woman, including difficulty bonding with her newborn and significant functional impairment, as well as for the family, such as the infant’s physical, emotional and mental development.”
These findings come from two double-blind, placebo-controlled, phase-3 studies, Hummingbird 202B and 202C, which examined the efficacy and safety of IV brexanolone (Sage Therapeutics), a proprietary formulation of allopregnanolone, in treating postpartum depression. The studies support a planned 2018 New Drug Application submission seeking FDA approval for brexanolone as the first pharmacotherapy specifically for postpartum depression.
Women aged 18 to 45 years with severe postpartum depression for 6 months or less at screening were randomly assigned (1:1:1) to receive brexanolone IV 90 g/kg/hour, brexanolone IV 60 g/kg/hour or placebo, administered as a continuous inpatient infusion for 60 hours. The investigators examined change in total depression score, using the Hamilton Rating Scale for Depression (HAM-D), from baseline at 60 hours. Efficacy and safety measures were analyzed for 30 days. In total, 122 women received brexanolone.
Participants who received brexanolone IV 90 g/kg/hour experienced a greater mean reduction in HAM-D score compared with placebo (17.7 points vs. 14 points; P = .0252) after 60 hours, as did those who received 60 g/kg/hour brexanolone (19.9 points; P = .0013). Furthermore, the effect observed at 60 hours was maintained at the 30-day follow-up.
Among participants receiving brexanolone IV, the investigators first noticed reductions in total depression score at 48 hours. They also observed improvements in the Clinical Global Impression-Improvement scale (CGI-I) at hour 60 among patients treated with brexanolone IV 90 g/kg/hour dose (P = .0095) and 60 g/kg/hour dose (P = .0131) relative to placebo. Brexanolone IV was generally well-tolerated; common adverse events included headache, dizziness and somnolence.
In the second trial, women diagnosed with moderate postpartum depression, based on a major depressive episode no earlier than the third trimester and no later than the first month following delivery, were randomly assigned (1:1) to receive brexanolone IV 90 g/kg/hour or placebo as a 60-hour inpatient infusion. The researchers measured the change in HAM-D score from baseline to hour 60, and efficacy and safety through day 30.
These data replicated the rapid and sustained effects of brexanolone IV observed in Hummingbird 202B. Overall, 104 women received the study drug. From baseline, there was a greater drop in HAM-D total score among participants treated with brexanolone IV at 60 hours (14.2 points) compared with placebo (12 points; P = .016). As in the first study, the investigators first noticed statistical significance at hour 48; this was sustained through 1 week. The mean reduction in depression score observed in the group receiving brexanolone IV at hour 60 remained at day 30.
Those treated with brexanolone IV showed greater improvement in the Clinical Global Impression-Improvement scale at hour 60 compared with those treated with placebo (P = .0005). Brexanolone was well-tolerated overall, and the most common adverse events were headache, dizziness and somnolence.
“There are currently no pharmacological therapies specifically approved for PPD and there is a clear unmet medical need for treatment,” Meltzer-Brody told Healio Psychiatry. “If approved, brexanolone will be the first FDA-approved drug indicated to treat PPD. The results seen in clinical trials with brexanolone have been profound and durable. In the trial, I saw patients living with severe PPD — disinterested in daily activity and disconnected from their families — improve significantly within days.” – by Savannah Demko
Meltzer-Brody SE, et al. Poster P5-168.
Meltzer-Brody SE, et al. Poster P5-169. Presented at: American Psychiatric Association Annual Meeting; May 5-9, 2018; New York.
Disclosures: Meltzer-Brody reports research grant funding from Sage and Janssen, and consulting for CME activities for Global Medical Education and WebMD/Medscape.