Zulresso (brexanolone) was granted approval from the US Food and Drug Administration (FDA), pending Drug Enforcement Agency (DEA) scheduling.
Sage Therapeutics’ therapy is the only drug specifically indicated for the treatment of postpartum depression (PPD), a life-threatening major depressive episode that occurs following childbirth and is characterized with decreased ability to feel pleasure, cognitive impairment, feelings of worthlessness or guilt, and/or suicidal ideation.
Administered through continuous IV infusion for 60 hours, Zulresso is only available through a restricted program. The Zulresso risk evaluation and mitigation strategy (REMS) program requires that the drug be administered by a health care provider in a health care facility, and patients be enrolled in the program prior to administration of the drug.
The treatment is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors – allosteric modulation of neurotransmitter receptor activity results in varied activity instead of complete activation or inhibition of the receptor.
Approval of Zulresso comes after efficacy of the treatment was shown in two clinical students in which participants received 60-hour continuous IV infusion of the drug or placebo. One study enrolled patients with severe PPD and the other enrolled patients with moderate PPD.
Efficacy was based upon the mean change of depressive symptoms by a depression rating scale, with Zulresso demonstrating superiority over placebo in both studies at the end of the first infusion. Improvement in depression was observed at the end of a 30-day follow-up period.
Due to the potential risk of serious harm from sudden loss of consciousness, patients must be monitored for excessive sedation while receiving the infusion. Additionally, patients must be accompanied during interactions with their child or children while receiving the infusion as part of the boxed warning present on the drug’s prescribing information.
Zulresso was also granted priority medicines (PRIME) designation from the European Medicines Agency.
Sage is developing a portfolio of product candidates for central nervous system (CNS) receptor systems. One candidate, Sage-217, is in Phase III development for the treatment of major depressive disorder and PPD.