The U.S. Food and Drug Administration's staff reviewers have expressed significant concerns about the efficacy of Otsuka Pharma's brexpiprazole combination therapy for post-traumatic stress disorder (PTSD), potentially jeopardizing the Japanese drugmaker's bid to expand treatment options for this debilitating mental health condition.
Regulatory Concerns Over Clinical Evidence
In briefing documents released Wednesday ahead of a Friday advisory panel meeting, FDA reviewers stated that the drug failed to demonstrate substantial evidence of effectiveness for PTSD when added to sertraline. The reviewers cited concerns about study design and inconsistent study results as primary reasons for their skepticism.
The FDA staff specifically highlighted that the combination therapy showed "inconsistent trial results and a modest treatment effect that may not be clinically meaningful." These concerns come as the agency prepares to convene its independent experts, who will make recommendations on whether to approve brexpiprazole in combination with Viatris' Zoloft for treating adults with PTSD.
Clinical Trial Data and Limitations
Otsuka's application was supported by data from one mid-stage and two late-stage studies testing the combination of brexpiprazole and Zoloft in PTSD patients compared to sertraline monotherapy. However, the regulatory review revealed significant weaknesses in this evidence base.
According to the FDA reviewers, one of the late-stage studies failed to show statistically significant differences in treatment response between the combination therapy and sertraline alone. Additionally, the mid-stage study was flagged for having "statistical and methodological concerns," further undermining the overall evidence package.
PTSD Treatment Landscape
PTSD is a mental health condition that can develop after a traumatic event, causing symptoms including flashbacks, nightmares and severe anxiety. The condition is estimated to affect about 4% of U.S. adults, according to the American Psychiatric Association, representing a significant unmet medical need.
Brexpiprazole, marketed under the brand name Rexulti, is currently approved in the U.S. to treat agitation in patients with Alzheimer's disease as well as for adults with major depressive disorder and schizophrenia. The drug is being co-developed by Otsuka and Danish drugmaker Lundbeck.
Regulatory Timeline and Next Steps
The FDA had originally planned to make a decision on Otsuka's PTSD treatment by February 8, but the agency delayed this timeline to seek input from its advisory panel on certain issues related to the marketing application. The agency has not set a new action date for the drug following the advisory committee meeting.
The Friday advisory panel meeting will be crucial in determining the path forward for this combination therapy, as the independent experts will weigh the available evidence and provide recommendations to the FDA on whether the benefits outweigh the risks for PTSD patients.
