FDA Advisory Committee Recommends Against Otsuka’s PTSD Treatment

FDA Panel Rejects Otsuka/Viatris PTSD drug Combination

ARCHYDE NEWS – In a critically important setback for Otsuka Pharma and Viatris, a key FDA advisory panel has overwhelmingly voted against the approval of a combination therapy for post-traumatic stress disorder (PTSD) involving Otsuka’s brexpiprazole and Viatris’s Zoloft (sertraline). The panel’s 10-1 vote aligns with FDA reviewers’ earlier assessments, concluding that the available data does not sufficiently demonstrate the drug combination’s effectiveness in treating PTSD in adults.

Otsuka’s submission was based on data from one interim and two late-stage studies that compared the combined treatment against sertraline plus a placebo. Notably, one of these pivotal late-stage trials failed to meet its primary endpoint, which was to significantly reduce the severity of PTSD symptoms.

“We simply cannot deny a negative study and say that we will approve it on the basis of two other positive studies,” stated Pamela Shaw, a biostatistician at Kaiser Permanente, echoing the panel’s concerns about the mixed trial results.

While acknowledging the potential of the combination for patients who don’t respond to sertraline alone, advisors also voiced concerns about the potential side effects of antipsychotics like brexpiprazole, especially weight gain and movement disorders associated with long-term use. “The big question for me is to know that antipsychotics can cause real problems, especially during long-term use, and the modest benefit that combined treatment can potentially offer,” commented Walter Dunn, deputy clinical professor of psychiatry at UCLA.

Otsuka has indicated it will continue to collaborate with the FDA as its request is reviewed. The agency, which initially had a decision deadline of Febuary 8, deferred its decision pending the advisory group’s input and has not yet set a new target date for action.The FDA typically, but not always, follows the recommendations of its expert advisors.

Had it been approved, this combination would have been the first new FDA-approved PTSD treatment in the U.S. in over two decades, following Zoloft and GSK’s Paxil.Brexpiprazole,marketed as Rexulti and co-developed by Otsuka and Lundbeck,is currently approved in the U.S. for agitation associated with Alzheimer’s disease, major depressive disorder, and schizophrenia.

What was the primary concern of the FDA advisory committee regarding brexpiprazole’s use for PTSD?

Understanding the Recent Advice for Brexpiprazole

On July 18, 2025, an FDA advisory committee delivered a negative recommendation regarding Otsuka Pharmaceutical’s brexpiprazole for the treatment of Post-Traumatic Stress Disorder (PTSD). this decision impacts the potential approval of a new PTSD medication and raises notable questions about the future of trauma-informed care. The committee’s vote was 9-6 against the benefits outweighing the risks,focusing on concerns about efficacy and potential side effects. This article will delve into the details of the recommendation, the drug itself, and what this means for individuals seeking PTSD treatment options.

What is Brexpiprazole?

Brexpiprazole is an atypical antipsychotic already approved by the FDA for the treatment of schizophrenia and as an add-on treatment for major depressive disorder. Otsuka sought to expand its use to include PTSD, citing promising results from clinical trials. The drug works by modulating serotonin and dopamine receptors in the brain, aiming to reduce symptoms like intrusive memories, negative mood, and hyperarousal associated with PTSD. Understanding antipsychotic medications and their mechanisms is crucial when evaluating this recommendation.

key Concerns Raised by the FDA Advisory Committee

The advisory committee’s decision wasn’t taken lightly. Several key concerns underpinned their recommendation against approval:

Limited Efficacy: While clinical trials showed some betterment in PTSD symptoms, the committee questioned the clinical significance of these improvements. Some members felt the benefits were marginal and not considerable enough to warrant approval, especially considering the potential risks.

side Effect Profile: Brexpiprazole,like other antipsychotics,carries a risk of side effects,including weight gain,akathisia (restlessness),and metabolic changes. The committee expressed concern that these side effects could outweigh the modest benefits for many patients. Antipsychotic side effects are a significant consideration in treatment decisions.

Trial Design & Patient Population: discussions centered around the design of the clinical trials and the characteristics of the patient populations studied.Some committee members felt the trials didn’t adequately represent the diversity of individuals living with PTSD.

Lack of Novelty: Several existing PTSD therapies are already available, including SSRIs and trauma-focused psychotherapy. The committee questioned whether brexpiprazole offered a significant advantage over these established treatments.

The Clinical Trial Data: A Closer Look

Otsuka presented data from two Phase 3 clinical trials involving over 300 participants diagnosed with PTSD. The trials measured changes in PTSD symptom severity using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).

Trial 1: Showed a statistically significant, but modest, improvement in CAPS-5 scores compared to placebo.

Trial 2: Demonstrated similar results, with a small but statistically significant difference between brexpiprazole and placebo.

However, the committee highlighted that the effect size was small, meaning the actual difference in symptom reduction between the drug and placebo was relatively minor. This is a critical point when evaluating the risk-benefit ratio of any medication.

What Happens Next? The FDA’s Decision Process

The FDA advisory committee’s recommendation is non-binding. The FDA will now review the committee’s feedback, along with all the data submitted by otsuka, before making a final decision on whether to approve brexpiprazole for PTSD.

FDA Review Timeline: The FDA typically makes a decision within three months of the advisory committee meeting. A decision is expected by October 2025.

Potential Outcomes: The FDA could:

Approve the drug as recommended by Otsuka.

Approve the drug with restrictions (e.g., a narrower patient population).

Reject the submission for approval.

Request additional data from Otsuka.

Implications for PTSD Treatment and Research

This recommendation has several implications for the field of PTSD treatment:

* Continued Need for Innovation: The lack of a