FDA Approves Zurzuvae, an Oral Treatment for Postpartum Depression

The Food and Drug Administration (FDA) has approved Zurzuvae^™ (zuranolone) for the treatment of postpartum depression (PPD) in adults.

Zuranolone is a neuroactive steroid gamma-aminobutyric acid (GABA)-A receptor positive allosteric modulator that is taken orally in the evening for 14 days. Prior to this approval, treatment for PPD was available only as an intravenous injection administered by a health care provider.

“Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings,” said Tiffany R. Farchione, MD, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research.

The approval was based on data from the NEST program, which included 2 randomized, placebo-controlled, double-blind studies evaluating Zurzuvae in adult women with PPD: SKYLARK (ClinicalTrials.gov Identifier: NCT04442503) and ROBIN (ClinicalTrials.gov Identifier: NCT02978326). The primary endpoint for both studies was the change from baseline in depressive symptoms as measured by the 17-item Hamilton Anxiety Rating Scale (HAMD-17) total score at day 15.

In SKYLARK, patients received Zurzuvae 50mg (n=98) or placebo (n=97). In ROBIN, patients received another zuranolone capsule approximately equivalent to 40mg of Zurzuvae (n=76) or placebo (n=74). Treatment was administered once daily in the evening with fat-containing food for 14 days. Dosage reduction was allowed based on tolerability. Patients were followed for a minimum of 4 weeks.

Findings showed that treatment with Zurzuvae led to a statistically significant improvement in depressive symptoms compared with placebo as measured by HAMD-17 total score. The placebo-subtracted difference was -4.0 (95% CI, -6.3, -1.7) in SKYLARK and -4.2 (95% CI, -6.9, -1.5) in ROBIN. This effect was reported to be maintained 4 weeks after the last dose of Zurzuvae (day 42).

The effect of nighttime administration of Zurzuvae on next morning driving performance was evaluated in 2 randomized, double-blind, placebo-, and active-controlled 4-way crossover studies. Findings showed that Zurzuvae did cause driving impairment due to central nervous system depressant effects.

A Boxed Warning included in the prescribing information advises that patients should not drive or engage in other potentially hazardous activities until at least 12 hours after administration. The warning also notes that patients may not be able to assess their own driving competence or the degree of impairment caused by Zurzuvae.

Adverse reactions commonly reported in clinical trials included somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection.

Zurzuvae is supplied in 20mg, 25mg, and 30mg capsules. The treatment is administered with a fat-containing food (eg, 400-1000 calories, 25% to 50% fat).

According to Sage Therapeutics and Biogen Inc, Zurzuvae is expected to become available in the fourth quarter of 2023 following scheduling as a controlled substance by the Drug Enforcement Administration.

The Companies also announced that the FDA has issued a Complete Response Letter (CRL) for the New Drug Application for zuranolone in the treatment of major depressive disorder (MDD). The letter states that additional data will be needed to support the approval of the drug for this indication.

Commenting on the FDA’s decision, Christopher A. Viehbacher, President and CEO at Biogen, said: “We believe that Zurzuvae will be an important option to treat PPD and we will thoroughly review the feedback from the FDA on the use of zuranolone in MDD to determine next steps.”