Sage Therapeutics’ brexanolone has cleared the bar of efficacy in two phase 3 trials in women with postpartum depression (PPD). The trials linked the intravenous formulation of allopregnanolone to statistically significant improvements on a depression scale, teeing Sage up to file for approval next year and sending its stock up 44%.

Investigators enrolled 122 patients with severe PPD in one of the phase 3 trials and 104 women with moderate forms of the condition in the other. Participants in both studies underwent infusion with either brexanolone or placebo.

In both trials, brexanolone delivered against the primary endpoint of change in Hamilton Rating Scale for Depression (HAM-D) from baseline. That is a big boost for Sage—which is still recovering from the failure of brexanolone in super-refractory status epilepticus—and raises hopes that a patient population with an unmet medical need will soon get a much-needed treatment option.

"PPD is commonly viewed as a disorder solely experienced by the mother, but it also seriously impacts the child and family members, both immediate and extended," Samantha Meltzer-Brody, M.D., primary investigator on the studies, said in a statement. "These data meaningfully advance our understanding of PPD and may prompt medical professionals to evaluate how PPD is perceived, identified and treated within their practices in the future."

Sage plans to file an NDA with the FDA next year.     

RELATED: Sage sags on phase 3 epilepsy med failure

The data contain a few blemishes that, while unlikely to derail the drug, raise questions about the extent to which it will improve the lives of people with PPD and where its peak sales will top out. 

While large enough to achieve statistical significance, the difference between the effect of the drug and placebo was smaller than that seen earlier in development. Such phase-to-phase dips happen in many development programs as the populations of patients being studied become larger and more diverse. But given that brexanolone requires patients and providers to commit to 60-hour in-clinic infusions, Sage needs compelling efficacy data to make its case for the drug.

There are questions about whether brexanolone clears that high bar, particularly in women with moderate forms of PPD. The trial in moderate patients, like that in subjects with severe PPD, met its primary endpoint. But, while brexanolone outperformed placebo over the first week, by day 30 there was no statistical difference between the treatment and control arms. 

Sage said the effect of brexanolone seen after 60 hours was maintained through the 30-day follow-up, suggesting the end of statistical significance is tied to improved outcomes in the placebo arm. Even so, doubts about durability could become a factor as Sage starts facing the regulatory and reimbursement challenges that stand between it and sales of brexanolone.