Sage Therapeutics Announces Brexanolone Eases Postpartum Depression in Two Phase 3 Trials

Brexanolone (earlier SAGE-547, Sage Therapeutics) has cleared the bar of efficacy in two phase 3 trials in women with postpartum depression (PPD).

The trials linked the proprietary intravenous formulation of Brexanolone on a depression scale seen statistically significant improvement, teeing Sage up to file for approval and sending its stock up 44% next year.

Investigators enrolled 122 patients with severe postpartum depression (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 demonstrated mean reductions from baseline in HAM-D total scores of 14 to 20 points at 60 hours maintained to 30 days brexanolone results showed well tolerated and a safety profile similar to that seen in earlier studies.

In both trials, brexanolone achieved against the primary endpoint of reduction in Hamilton Rating Scale for Depression (HAM-D) from baseline compared to placebo at 60 hours. That is a big rise for Sage which is still improving from the failure of brexanolone in super-refractory Status epilepticus (SE) and it raises hopes to the patient population with an unfulfilled medical need will soon get a much-needed treatment option.

PPD is a disorder experienced by the mother solely, but it impacts the child and family members seriously.” Samantha Meltzer-Brody, M.D., MPH, associate professor and director of UNC Perinatal Psychiatry Program of the UNC Center for Women’s Mood Disorders and primary investigator on the studies, said in a statement. “It is meaningfully advancing our understanding of PPD in these studies and may prompt medical professionals to evaluate how PPD is anticipated and treated within their practices in the future.”

In the next year, Sage plans to file a New Drug Application (NDA) with the Food and Drug Administration (FDA).

In Study 202B, patients with severe PPD (N = 122) were randomized to one of three treatment groups, contain a few blemishes that, while unlikely to cause the drug, raise questions about to which extent 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 reductions in HAM-D total score of brexanolone versus placebo was first observed at 48 hours and the effect at 60 hours was smaller than that seen earlier in development was maintained through the 30-day follow-up with statistical significance for both brexanolone dose groups. In many development programs, such phase-to-phase dips happen as the populations of patients being studied become larger and more diverse. But it is given as 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 particularly in women with moderate forms of PPD, whether brexanolone clears that high bar or not. The trial in moderate patients with severe PPD, it met the primary endpoint. But, over the first-week brexanolone outperformed placebo, there was no statistical difference between the treatment and control arms by day 30.

Nonetheless, Sage starts facing the regulatory and reimbursement challenges because of doubts about durability could become a factor as that stands between it and sales of brexanolone.

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