As the U.S. Food and Drug Administration (FDA) advisory committee prepares to meet on July 18 to review brexpiprazole (marketed as Rexulti) combined with sertraline for treating post-traumatic stress disorder (PTSD) in adults, FDA reviewers have flagged significant concerns about the drug’s effectiveness.
In their briefing document, FDA reviewers described the study results as “discordant,” highlighting that in the fixed-dose study using 2 mg and 3 mg doses of Rexulti, neither dose showed superiority compared to the combination of sertraline and placebo.
The reviewers concluded that this study was a clear negative, failing to demonstrate statistical significance in either its primary or secondary outcomes.
The supplemental New Drug Application (sNDA) also included results from a phase 2 trial that was randomized, double-blinded, and placebo- and active-controlled.
While a post-hoc analysis of this trial suggested Rexulti combined with sertraline had statistical benefits over sertraline plus placebo, FDA reviewers expressed skepticism. They pointed out that these comparisons did not align with the primary objectives of the study, casting doubt on the overall findings.
This scrutiny adds to the challenges in finding new effective treatments for PTSD, a condition that has seen no new approved therapies in over two decades despite a critical need. The FDA recently declined approval of MDMA-assisted therapy for PTSD pending further phase 3 safety and efficacy trials, underscoring the agency’s caution.
Rexulti is already approved for other conditions such as adjunctive treatment for major depressive disorder, schizophrenia, and agitation in Alzheimer’s disease dementia.
It acts on multiple brain receptors involved in mood and cognition, including norepinephrine, serotonin, and dopamine receptors. However, the exact mechanism by which it might help PTSD remains unclear.
The upcoming advisory committee meeting will weigh these concerns and the available evidence before making a recommendation. Even if the committee advises against approval for Rexulti in combination with sertraline for PTSD, the FDA is not obligated to follow their guidance.
The debate around Rexulti’s potential as a PTSD treatment highlights the ongoing difficulty in developing safe and effective therapies for this challenging mental health condition.
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