In March 2019, the small molecule brexanolone was approved by the United States Food and Drug Administration (FDA) for the treatment of postpartum depression (PPD) in adult women.[1] Brexanolone, developed by Sage Therapeutics under a license from the University of California, was granted priority review status and breakthrough therapy designation by the FDA.[2][3]

Brexanolone is an intravenous neuroactive steroid that is administered continuously over a 60-hour period.[1] It acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors.[1]  While the mechanism of action of brexanolone is not fully understood, this drug is the first to be approved by the FDA for the specific treatment of PPD. [1]

This agent was approved based on data from the Hummingbird study, which included two phase III trials (NCT02942004 and NCT02942017). [1] Both trials were multicenter, randomized, double-blind, parallel-group, placebo-controlled studies of the efficacy, safety, and pharmacokinetics of the IV injection.[4][5] Dose-ranging of brexanolone in a total of 138 patients with severe PPD in the United States and New Zealand was evaluated in clinical trial NCT02942004.[2][4] The NCT02942017 trial enrolled a total of 108 patients with moderate PPD in the United States and New Zealand. The primary endpoint was met in both trials; there was a significant mean reduction from baseline in the Hamilton Rating Scale for Depression total score at 60 hours compared with placebo.[2]

Jeff Jonas, M.D., Chief Executive Officer of Sage Therapeutics states, “[Brexanolone] will address an important need for women’s mental health, the impact of PPD is multi-generational, and we look forward to bringing [brexanolone] to patients in urgent need of a new treatment option. We believe [brexanolone] will be a catalyst in starting a new dialogue emphasizing the importance of women’s mental health, and the importance of diagnosing and treating PPD.”[6]

A common, yet often undiagnosed, medical complication occurring during pregnancy or after childbirth, PPD is a major depressive episode that may negatively impact the mother, her relationship with a partner, and the infant’s physical, mental, and emotional development.[7] Common symptoms of PPD include avoiding friends or family, losing interest in activities, thoughts of harming oneself or one’s baby, and feeling sad, hopeless, empty, overwhelmed, worried, or overly anxious.[7]

To Professor Samantha Meltzer-Brody, M.D., M.P.H., the primary investigator of the brexanolone clinical trials, the approval of brexanolone “represents a game-changing approach to treating PPD.” According to Professor Meltzer-Brody, “The potential to rapidly reduce symptoms in this critical disorder is an exciting milestone in women’s mental health. PPD is recognized to have a significant and long-term impact on women and their families, but […] we may finally have the opportunity to change that.”[6]

Notably, the prescribing information for brexanolone carries a boxed warning for excessive sedation and sudden loss of consciousness.[8] As a result of these risks, brexanolone has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available through a restricted program called Zulresso REMS; this program requires the drug to be administered by a health care provider in a certified health care facility.[3][8]

A phase III trial (NCT 03665038) to evaluate the safety and efficacy of brexanolone in the treatment of PPD in adolescent females aged 15 to 17 years is ongoing in the United States. [1][9]

For additional information related to the first global approval of brexanolone please visit Drugs[1], or to learn more about the overall development of this drug across all indications visit AdisInsight[2].

Image credit: Suhyeon Choi – Unsplash

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