Phase 3 Results Show SAGE-217 Treats Postpartum Depression Successfully

Topline results from the phase 3 ROBIN Study of SAGE-217 for depressive symptoms in women with postpartum depression (PPD) indicate promising efficacy and safety.

Patients treated with SAGE-217 for 2 weeks had a statistically significant improvement of 17.8 points on the Hamilton Rating Scale for Depression (HAMD-17) score, compared to 13.6 for placebo (P = .0029), meeting the study’s primary endpoint.

“These are strong and consistent data demonstrating a rapid, stable, and clinically meaningful improvement in PPD depressive symptoms in the SAGE-217 treatment group compared to placebo,” said Jeff Jonas, MD, chief executive officer of Sage Therapeutics, in a statement.

The ROBIN study included 151 patients aged 18 to 45 years with severe postpartum depression. Participants were randomized to either daily SAGE-217 30 mg or placebo for 2 weeks.

The ROBIN study was designated as pivotal in June 2018 following a meeting with the FDA where SAGE-217 was granted Breakthrough Therapy designation for the treatment of major depressive disorder.

Differences in the reduction of HAMD-17 scores between SAGE-217 and placebo became statistically significant on Day 3 (-12.5 vs. -9.8; P = .0255) and this was maintained through the 2 weeks of treatment as well as through the 4-week follow-up visit (-19.2 vs. -15.1; P = .0027).

After 2 weeks of treatment, 45% of patients treated with SAGE-217 achieved remission as measured by HAMD-17, compared to 23% of patients receiving placebo (P = .0122). At the end of the 4-week follow-up, those rates were 53% and 30%, respectively (P = .0102).

After 2 weeks of treatment, 72% of patients in the SAGE-217 arm achieved a response, defined as a 50% improvement in baseline HAMD-17 score, compared to 48% of patients in the placebo arm (P = .0050). At 4 weeks, those rates increased to 75% and 57%, respectively (P = .0220).

The study reported a similar rate of adverse events for both SAGE-217 (58%) and placebo (51%) groups. A participant in each group experienced a serious adverse event (SAE). The SAE in the SAGE-217 arm was resolved with a dose reduction. One patient in the treatment arm discontinued study participation due to an adverse event.

The most common adverse events with ≥5% incidence in either treatment arm were somnolence (12.8% SAGE-217; 8.2% placebo), headache (9.0% SAGE-217; 12.3% placebo), dizziness (7.7% SAGE-217; 5.5% placebo), upper respiratory tract infection (7.7% SAGE-217; 1.4% placebo), diarrhea (6.4% SAGE-217; 2.7% placebo), nausea (3.8% SAGE-217; 8.2% placebo), sedation (5.1% SAGE-217; 0.0% placebo), vomiting (1.3% SAGE-217; 5.5% placebo), abnormal dreams (0.0% SAGE-217; 5.5% placebo) and hyperhidrosis (0.0% SAGE-217; 5.5% placebo).

“This is our fifth consecutive positive study in mood disorders with our investigational medicines that utilize our innovative approach to GABA receptor modulation,” added Jonas. “Data from the ROBIN Study, along with earlier data from our studies with Zulresso in PPD and SAGE-217 in major depressive disorder, all point to the promise that our approach may hold—not only in changing the way PPD and MDD are treated, but also in potentially improving the lives of patients suffering from these mood disorders.”