FDA Raises Concerns Over Rexulti's Efficacy in PTSD Treatment

The U.S. Food and Drug Administration (FDA) has expressed doubts about the efficacy of Rexulti (brexpiprazole) in treating post-traumatic stress disorder (PTSD), casting uncertainty over Otsuka and Lundbeck's application to expand the drug's label. The concerns come ahead of a crucial advisory committee meeting scheduled for Friday, where experts will weigh in on the conflicting results from clinical trials.

Discordant Trial Results Complicate Rexulti's PTSD Bid

Otsuka and Lundbeck are seeking approval for a combination therapy of Rexulti with sertraline (Zoloft) for PTSD treatment. However, FDA reviewers have highlighted "discordant results" from two Phase III trials conducted by the companies. In a briefing document released prior to the advisory committee meeting, the agency noted that one study using fixed doses of Rexulti (2 mg and 3 mg) failed to demonstrate superiority over sertraline plus placebo.

The FDA described this study as "clearly and convincingly a negative study that did not demonstrate statistical significance on its primary or secondary endpoints." In contrast, a second Phase III trial using flexible dosing of Rexulti (2 mg or 3 mg) showed positive results, complicating the interpretation of the overall efficacy evidence.

To bolster their application, Otsuka and Lundbeck submitted additional data from a Phase II study. However, FDA reviewers expressed concerns about the retrospective selection of comparisons from this trial, stating that they "do not align with the study's primary objectives" and raise issues regarding the inflation of false positive rates.

Regulatory Implications and Market Outlook

The FDA's Psychopharmacologic Drugs Advisory Committee will convene on Friday to discuss these concerns and provide recommendations on the application. As a result of these developments, the FDA has delayed its decision on Rexulti beyond the original target action date of February 8, 2025, with no new date announced.

Rexulti, an atypical antipsychotic, is currently approved for schizophrenia and major depressive disorder. The drug has shown strong market performance, with Lundbeck reporting first-quarter revenues of 1.5 billion Danish kroner ($233 million), representing a 28% increase at constant exchange rates. The potential expansion into PTSD treatment could significantly impact the drug's market position and the companies' growth strategies.

Otsuka's Pipeline Expansion Amid Regulatory Challenges

While facing regulatory hurdles with Rexulti, Otsuka continues to strengthen its pipeline through strategic acquisitions. The company recently acquired Cantargia's investigational anti-IL-1RAP, CAN10, for several autoimmune conditions. The deal involves a $33 million upfront payment and up to $580 million in potential milestone payments, highlighting Otsuka's commitment to diversifying its portfolio and addressing unmet medical needs.