• 22 Sep 2025
• Admin
• News Article

FDA Rejects Otsuka & Lundbeck’s PTSD sNDA for Rexulti + Sertraline

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the supplemental New Drug Application (sNDA) for Rexulti (brexpiprazole) in combination with sertraline for the treatment of post-traumatic stress disorder (PTSD) in adults.

The FDA stated that the application does not provide substantial evidence of effectiveness to support approval.

Background on the sNDA

• The application was accepted for review in June 2024.
• It was based on three randomized clinical trials evaluating safety and efficacy of Rexulti + sertraline in adults with PTSD.
• On July 18, 2025, the Psychopharmacologic Drugs Advisory Committee voted 1–10 against the efficacy of the combination therapy, concluding the data did not demonstrate clinical benefit.

The FDA confirmed that not all of the submitted trials contribute to “substantial evidence” and that additional, well-controlled positive studies would be required for approval.

Company Responses

John Kraus, M.D., Ph.D., EVP & Chief Medical Officer, Otsuka:

“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. Otsuka and Lundbeck will take time to review the contents of the letter with the FDA to determine the appropriate path forward.”

Johan Lutham, EVP, Lundbeck R&D:

“Post-traumatic stress disorder places a significant and often overlooked burden on patients, their families, and society. We are grateful to the participants, their families, the clinical trial site investigators and staff, and the entire program team for their dedication.”

About Rexulti (Brexpiprazole)

• U.S. Approvals:
  - 2015: Adjunctive therapy to antidepressants for major depressive disorder (MDD); treatment for schizophrenia in adults.
  - 2023: Treatment for agitation associated with Alzheimer’s disease dementia.
• Global Approvals: Approved in 60+ countries, including the EU, Canada, and Japan.
• Mechanism of Action: Not fully understood. Brexpiprazole is:
  - Antagonist at norepinephrine α1B/α2C and serotonin 5-HT2A receptors.
  - Partial agonist at serotonin 5-HT1A and dopamine D2 receptors.

Company Overview

• Otsuka Pharmaceutical Co., Ltd.: A total healthcare company advancing diagnostics and treatments for both physical and mental health.
• H. Lundbeck A/S: Global biopharma focused on brain health, co-developing Rexulti with Otsuka.

Takeaway: The FDA’s decision is a setback for Otsuka and Lundbeck’s push into PTSD, reinforcing the agency’s requirement for robust efficacy evidence before approving psychiatric indications.