An advisory panel to the FDA has recommended the approval of brexanolone (Zulresso), Sage Therapeutics’ experimental treatment for postpartum depression (PPD). The panel voted 17-1 in favor of the injectable treatment, Zulresso saying its benefits outweighed the risks.
There are currently no FDA-approved drugs to specifically treat postpartum depression, a much more extreme version of the so-called “baby blues” some women experience after childbirth. If given the green signal by FDA brexanolone would become the first drug to 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.
Owing 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 analog 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 two “no” votes on the safety question focused on the part that asked whether, in addition to the applicant adequately characterizing the safety profile of brexanolone, the loss-of-consciousness events have been “characterized sufficiently” to enable its safe use.
The agency also discussed certifying that healthcare facilities are capable of doing monitoring and that the facility must attest that only nurses, such as RNs or LPNs, will be administering the drug.
But other committee members disagreed, arguing that perhaps the availability of the drug should be extended to alternative sites, such as infusion centers, “well-equipped” pharmacies, or even sleep labs. Several members conjured up dueling images of sensational stories in the media related to accessibility of the drug.
The committee also debated potential dosing for the drug — 90 μg/kg/hr, with an option to decrease based on tolerability, or 60 μg/kg/hr, with an option to increase based on the response. The committee concluded there was not enough evidence to make a decision and left it to the FDA to decide, though most people with an opinion favored the initial 90 μg/kg/hr dose, based on “clinical judgment.”
They also advised to further examine data in patients with psychosis, as well as an observational study in a large sample to confirm more about the safety risk, as well as which specific groups of patients could benefit from reduced hours and dosage of the drug.
The FDA does not have to follow the advice of its advisory committees, but it often does. In this case, one agency representative told the committee that, “I can’t think of another meeting where we will actually leave with more to think about than when we came in.”
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