Phase 2 study results show efficacy, safety of SAGE-547 for postpartum depression

Recent findings indicated that SAGE-547, an IVtreatment for postpartum depression, was safe and effective among women who developed severe depression during or following childbirth.

“This is potentially one of the most important clinical findings in the pharmacologic treatment of postpartum depression to date,” study researcher Samantha Meltzer-Brody, MD, MPH, of the University of North Carolina, said in a press release. “The rapid onset of action of this drug observed in the trial is unlike anything else available in the field to date. The data show the potential of the drug to provide relief from the debilitating symptoms of [postpartum depression], and to markedly decrease suffering in women who are severely affected.”

To assess efficacy of SAGE-547, an allostetric modulator of synaptic and extra-synaptic GABA_A receptors, for postpartum depression, researchers conducted a phase 2, multicenter, placebo-controlled, double-blind trial among 32 women with severe postpartum depression, as indicated by Hamilton Depression Rating Scale (HAM-D) scores of 26 and higher. Study participants developed severe depression either in the third trimester or within 4 weeks of childbirth.

Sixty hours after treatment, women who received SAGE-547 had a mean reduction in HAM-D scores greater than 20 points, with a difference of 12 points or more compared with placebo (P = .008).

Statistically significant differences in treatment effect began at 24 hours (P = .006) and was maintained through the 30-day follow-up (P = .01).

At 60 hours, depression remission, indicated by HAM-D scores of 7 or less, was observed in seven of 10 women who received SAGE-547, compared with one of 11 who received placebo (P = .008).

At 30 days, seven of 10 women who received SAGE-547 were in remission, compared with two of 11 who received placebo (P = .03).

Montgomery-Åsberg Depression Rating Scale (MADRS) scores indicated similar findings. Significant differences in scores were observed at 24 hours (P = .004) and were maintained to 30 days (P = .01).

At 60 hours post-treatment, mean change in baseline MADRS total scores were –27.9 among the SAGE-547 group, compared with –12.2 among the placebo group, indicating a treatment difference of 15.7 points (P = .01).

No serious adverse events occurred during treatment and follow-up periods, according to the release. Adverse events were more commonly reported in the placebo group vs. the treatment group.

“There has been a long-standing need to find an effective treatment option for women with postpartum depression, not only to alleviate the suffering of those women struggling with the disease, but to mitigate the effect on their family and children. We believe these data represent an unprecedented opportunity for developing treatments for [postpartum depression] ... and will serve as a paradigm shift in how the disease is thought about and ... how [postpartum depression] might be treated in the future,” Stephen J. Kanes, MD, PhD, chief medical officer of Sage Therapeutics, said in the release. “The results of this study replicate and extend the findings of our original, open-label probe study of [postpartum depression] reported previously. Given the consistent activity signals seen in both our open-label and placebo-controlled trials, we also intend to examine the development pathways for several of our other proprietary pipeline compounds into the treatment of a variety of psychiatric disorders, such as major depression, bipolar disorder and panic disorder.”

Sage Therapeutics is expanding the phase 2 trial to determine optimal dosing of SAGE-547. Study enrollment will begin before the end of 2016.