Sage Therapeutics' lead antidepressant brexanolone generated positive results in two phase III trials for postpartum depression, and a next-generation candidate with similar properties passed a smaller phase II trial for major depressive disorder.

Brexanolone is an intravenous formulation of the steroid allopregnanolone, which is thought to affect mood by acting as a positive allosteric modulator of the GABAA receptor. In November, two phase III trials of the drug in 226 women with postpartum depression met the primary end point of reduction of Hamilton Rating Scale for Depression (HAM-D) scores at 60 hours. Treatment reduced HAM-D scores by 14–20 points, compared to reductions of 12–14 points by placebo.

The treatment effect was modest compared with the 12-point difference that was observed during phase II trials. But the company pointed to the rapid onset of action as a major selling point for the drug, and the firm's share price jumped by 50% on these results. The HAM-D reduction with brexanolone was maintained at 30 days, but was no longer significantly different to placebo at this time point, a failure that the company attributed to variability in the placebo arm.

The company plans to file for regulatory approval of the drug in 2018.

These findings were bolstered in December by phase II results with SAGE217, which has similar properties to brexanolone but is orally available. In an 89-patient phase II trial, SAGE217 reduced HAM-D scores by 18 points at day 15, compared with a reduction of 11 points for placebo. By week 6, the effect was no longer statistically different. Sage's share price jumped again on these results, by another 70%, to US$161.

Phase II trials of SAGE217 in essential tremor and in Parkinson disease are ongoing. Brexanolone failed in a pivotal epilepsy trial earlier this year, despite promising prior phase II results in this indication.