FDA Rejects REXULTI® for PTSD, Citing Lack of ‘Substantial Evidence’ of Efficacy

The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Otsuka Pharmaceutical and H. Lundbeck, denying approval for their supplemental New Drug Application (sNDA) for REXULTI® (brexpiprazole). The companies had sought approval for REXULTI to be used in combination with sertraline for the treatment of Post-Traumatic Stress Disorder (PTSD) in adults.

The FDA’s decision, which follows a July 2025 advisory committee meeting where a panel voted 1-10 against the drug’s effectiveness, stated that the submitted data did not provide substantial evidence of effectiveness. The sNDA was based on three randomized clinical trials, but the FDA’s CRL indicated that additional positive, well-controlled trials would be necessary for any future approval.

Company and Expert Reactions

Despite the setback, both companies expressed their continued belief in the drug’s potential. Dr. John Kraus, Otsuka’s chief medical officer, stated that the companies will review the letter to determine a path forward. Johan Luthman, executive vice president of Lundbeck Research & Development, highlighted the significant burden of PTSD on patients and society, expressing gratitude to the trial participants for their dedication.

Understanding REXULTI® and PTSD

Current Indications: REXULTI (brexpiprazole) is currently FDA-approved for several other conditions. Since its initial approval in 2015, it has been used as an adjunctive therapy for adults with major depressive disorder (MDD) and as a treatment for schizophrenia. In May 2023, it was also approved for the treatment of agitation associated with dementia due to Alzheimer’s disease.
About PTSD: PTSD is a common mental health disorder affecting approximately 5% of the U.S. population annually. It can result from experiencing or witnessing traumatic events, such as physical assault, natural disasters, or war. PTSD can present with symptoms that interfere with daily life and may require long-term treatment.