Zurzuvae

Zurzuvae (zuranolone) is a drug reviewed under NDA 217369. The proposed treatment duration for zuranolone is 14 days. Efficacy studies primarily used the HAMD-17 as an outcome measure.

In efficacy trials, zuranolone demonstrated a HAMD-17 total score change from baseline of approximately 4 points (PPD-301 & PPD-201B). The HAMD-17 response rate was 71.6%, and the HAMD-17 remission rate was 44.6%. For the HAM-A total score, zuranolone showed a change from baseline of -12.8, with a mean treatment difference versus placebo of -2.2. The MADRS total score change from baseline was -19.7, with a mean treatment difference versus placebo of -5.1. The CGI-I response rate (very much improved or much improved) was 66.7%, with an odds ratio versus placebo of 2.232.

Safety findings include a relative infant dose of zuranolone in breast milk of 0.357%. The maternal NOAEL for general toxicity and NOAEL for growth and development in offspring were both 1 mg/kg/day. Zuranolone exhibited 23% hERG channel inhibition at 3 µM. QTc effects were observed at 7.1-fold exposures versus clinical mean Cmax (50 mg), and pulmonary function effects at 3-fold exposures versus clinical mean Cmax (50 mg).