Biogen Inc. — Zurzuvae FDA Review (NDA217369, ORIG 2, 2023)

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This integrated FDA review of ZURZUVAE (zuranolone) for Major Depressive Disorder (MDD) and Postpartum Depression (PPD) details its development, pharmacology, toxicology, and clinical data. Zuranolone, a novel GABAA positive allosteric modulator, demonstrated rapid and durable efficacy in PPD in two placebo-controlled trials. Key safety concerns include CNS depressant effects (somnolence, dizziness, sedation), leading to driving impairment, and embryo-fetal toxicity, which will be addressed in labeling with a boxed warning. Other safety considerations include suicidal ideation, abuse potential (comparable to alprazolam), and potential for physical dependence. Pharmacokinetic studies informed dose selection and adjustments for renal/hepatic impairment. While no significant hepatotoxicity or QT prolongation was found, extensive warnings regarding CNS depression are recommended. Carcinogenicity studies showed no significant tumor increases.

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