FDA approves Sage-Biogen oral postpartum depression drug

Aug. 7, 2023

Late last week, the FDA approved the first oral drug designed to treat postpartum depression (PPD) in adults, developed by Biogen and Sage Therapeutics.  

Branded Zurzuvae, the drug is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). It is taken orally once-daily for 14 days, providing an alternative to Sage’s Zulresso, an intravenous injection treatment for PPD first approved in 2019

The oral and intravenous treatments approved for PPD are derived from allopregnanolone, a neuroactive steroid produced in the body from progesterone. During pregnancy, its levels increase significantly and decline rapidly after childbirth, possibly contributing to postpartum depression. The drugs therapeutic mechanism is to restore these levels. 

While the partners' approval was a win, the FDA responded to the larger indication — major depressive disorder — with a Complete Response Letter. The CRL indicated that the application lacked sufficient evidence of effectiveness to justify the approval of Zurzuvae for MDD treatment, and asked the companies to hold additional studies.

While it provided some benefit in two late-stage MDD studies, there have been concerns about its effectiveness and durability. Critics were skeptical of study results released in June 2021 from a phase 3 WATERFALL study in major depressive disorder showed only a small-to-moderate efficacy benefit over the placebo, and a waning benefit over time.

Sage signed a deal worth up to $1.5 billion with Biogen back in Nov. 2020 to co-develop and co-commercial both zuranolone and another Sage asset, SAGE-324, for essential tremor and other neurological disorders.