FDA Rejects Lundbeck and Otsuka's Rexulti for PTSD Treatment

The U.S. Food and Drug Administration (FDA) has issued a complete response letter to Lundbeck and Otsuka Pharmaceutical, denying approval for their atypical antipsychotic Rexulti (brexpiprazole) in combination with Viatris' Zoloft (sertraline) as a treatment for post-traumatic stress disorder (PTSD). The decision follows a negative recommendation from an FDA advisory committee earlier this year and marks a significant setback for the pharmaceutical partners in their efforts to expand Rexulti's indications.

Efficacy Concerns Lead to FDA Rejection

According to the companies, the FDA cited a lack of substantial evidence of effectiveness in PTSD as the primary reason for the rejection. The regulatory agency's decision was based on its review of three phase 3 trials submitted by Lundbeck and Otsuka to support their application. The FDA indicated that "not all of these studies are capable of contributing to the substantial evidence of the submission," suggesting that the data presented was insufficient to demonstrate the drug's efficacy in treating PTSD.

The complete response letter from the FDA advises that additional clinical trials will be necessary to establish stronger efficacy data if the companies wish to pursue approval for Rexulti in PTSD. This requirement aligns with the concerns raised during the FDA advisory committee meeting in July, where outside experts voted 10 to 1 against recommending approval, arguing that the existing clinical data did not sufficiently support the combination's efficacy.

Impact on Rexulti's Market Position

Despite this setback, Rexulti continues to perform well in its currently approved indications. The drug holds approvals for major depressive disorder, schizophrenia, and agitation associated with Alzheimer's disease dementia. Lundbeck reported total 2024 sales of Rexulti at 5.2 billion Danish kroner (approximately $822 million), representing a 16% increase at constant currencies.

The rejection for PTSD limits Rexulti's potential market expansion in the near term. PTSD affects an estimated 5% of the U.S. population, according to the National Center for PTSD, representing a significant unmet medical need. The current treatment landscape for PTSD primarily consists of selective serotonin reuptake inhibitors (SSRIs) such as Zoloft and Paxil (paroxetine), both of which have been available as generics for years.

Future Outlook and Company Response

Despite the setback, both Lundbeck and Otsuka appear committed to exploring Rexulti's potential in PTSD. John Kraus, M.D., Ph.D., Otsuka's Executive Vice President and Chief Medical Officer, stated, "While we respect the FDA's decision, we continue to believe in the potential of Rexulti in combination with sertraline to help address this serious unmet need." The companies have indicated that they will review the contents of the FDA's letter to determine the appropriate path forward, which may include conducting additional clinical trials to address the efficacy concerns raised by the regulatory agency.