A phase 3 trial of Sage Therapeutics’ oral treatment for postpartum depression (PPD) has met its primary endpoint. The trial linked the drug, SAGE-217, to sustained, statistically significant improvements on a depression score and saw no cases of fainting.
Sage is closing in on an FDA approval of its lead PPD drug, brexanolone, but will likely find the market opportunity for the asset constrained by its 60-hour infusion time. SAGE-217, like brexanolone, is an allosteric modulator of GABAA receptors. The big difference is SAGE-217 is a once-daily oral product, making it far more convenient to take than brexanolone.
A phase 3 trial of SAGE-217 suggests the convenience has not come at the cost of safety or efficacy. Across 151 women with severe PPD, SAGE-217 outperformed placebo against multiple measures of depression, including the Hamilton Rating Scale for Depression (HAMD-17) score.
After two weeks of treatment, the HAMD-17 scores of women in the treatment arm had improved by 17.8, compared to 13.6 in the placebo cohort. That finding resulted in the trial hitting its primary endpoint with a p value of 0.0029. The HAMD-17 scores in the two arms diverged statistically after three days of treatment and the difference was maintained through the four-week follow-up.
SAGE-217 outperformed placebo against secondary endpoints, too. Statistically more patients in the SAGE-217 arm were in remission or had a 50% or greater HAMD-17 improvement after two and four weeks. SAGE-217 performed better on the Montgomery-Åsberg Depression Rating Scale, too.
The readout will also go some way to countering concerns about the safety of SAGE-217. Specifically, no participants lost consciousness in either cohort. A potential link between SAGE-217 and fainting was one cause for concern for Sage and its supporters going into the phase 3 readout.
Sage’s positive PPD data are an important moment for SAGE-217 and efforts to treat depression. Just how important SAGE-217 is will become clearer as Sage delivers more data from its phase 3 program. Sage is currently gearing up to test SAGE-217 in two clinical trials that will enroll patients with major depressive disorder. The larger of the two trials is due to finish in November.
Shares in Sage rose 38% in premarket trading.