Magnitude of effect called ‘groundbreaking’ by one advisor.
An FDA advisory committee voted overwhelmingly to recommend approval for brexanolone, the first drug that would be specifically approved for patients with postpartum depression.
Members of the FDA’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 18-0 on whether the sponsor, Sage Therapeutics, demonstrated efficacy of the drug, 16-2 on whether it had demonstrated adequate safety data (and whether concerns about certain adverse events were characterized sufficiently to enable safe use), and 17-1 on whether the benefits outweighed the risks.
At the meeting, committee members praised the treatment, calling it an “exciting breakthrough,” giving “enthusiastic yes” votes, with one member saying that “probably since the approval of Prozac, this [would be] one of the greatest approvals ever.” Members were mostly united on efficacy, safety, and that the benefits of brexanolone outweighed the risks for the treatment of postpartum depression, citing the intense need for therapy in this population.
The public comment portion lasted almost an hour, as the committees heard testimony from patients, mental health, and/or postpartum depression advocates, including principal investigators and patients from the brexanolone trials.
But due to concerns from the FDA and some members of the committee about adverse events — including six patients out of 140 with observed loss of consciousness/pre-syncope during the infusion, the agency recommended implementing a Risk Evaluation and Mitigation Strategy (REMS) to improve the product’s safety.
Brexanolone was described by the FDA in briefing documents as a “proprietary analogue of the endogenous human hormone allopregnanolone.” In the trials, it was administered as a 60-hour intravenous infusion. The sponsor, Sage Therapeutics, presented three clinical trials with a primary endpoint of a change in baseline on the Hamilton Depression Scale (HAM-D) at 60 hours. In all three trials, the agency said, brexanolone had a greater effect on HAM-D than did placebo.
“The results were consistent, the magnitude of the effect was large with a novel therapy that was, quite frankly, groundbreaking,” committee member Jess G. Fiedorowicz, MD, of the University of Iowa Carver College of Medicine, said.