A few weeks ago, Biogen and Sage Therapeutics announced that they have completed a rolling submission to the FDA of a New Drug Application (NDA) for zuranolone for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). The investigational drug is being evaluated as a rapid-acting, once-daily, 14-day oral short course therapy for adult patients with MDD and PPD.
Zuranolone is similar to brexanolone, which was approved in 2019 by the FDA for the treatment of PPD, and is a neuroactive steroid with a novel mechanism of action as a positive allosteric modulator of GABA-A receptors.
Data from the Phase 3 SKYLARk study demonstrated that a 15-day course of zuranolone was superior to placebo in women with severe PPD. By day 3, women receiving zuranolone experienced a greater reduction in HAM-D scores than women receiving placebo (mean reduction, 9.5 vs 6.1; P = 0.0008). The difference in mean HAM-D scores steadily increased up to day 15. At day 15, the mean reduction in HAM-D scores was 15.6 in women receiving zuranolone vs. 11.6 in the placebo group (difference -4.0; P = 0.0007). At day 45, women treated with zuranolone continued to show a greater reduction in HAM-D scores compared to women receiving placebo.
This is exciting. If zuranolone is approved, we would have a rapidly acting antidepressant with a good safety profile. Zuranolone was generally well-tolerated; the most common adverse events (AEs) included headache, somnolence, dizziness, and sedation. While the SKYLARK study looked specifically at the treatment of depression in postpartum women, other studies included in the LANDSCAPE clinical development programs indicated that zuranolone is effective in women and men with non-postpartum episodes of major depressive disorder.
Ruta Nonacs, MD PhD