Otsuka Pharmaceutical Co., Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announce that Otsuka has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the supplemental New Drug Application (sNDA) for use of REXULTI^® (brexpiprazole) in combination with sertraline for the treatment of adults with post-traumatic stress disorder (PTSD). The CRL states that the FDA has completed their review but cannot approve the application in the current form, further stating that the application does not provide substantial evidence of effectiveness to support the approval.

The sNDA for brexpiprazole in combination with sertraline for the treatment of adults with PTSD was accepted for review by the FDA in June 2024 and was based on data from three randomized clinical trials that evaluated the safety and efficacy of brexpiprazole in combination with sertraline in adult patients with PTSD.

The FDA decision follows a meeting of the Psychopharmacologic Drugs Advisory Committee on July 18, 2025. The committee voted 1-10, determining that the efficacy of brexpiprazole, when initiated concurrently with sertraline, has not been established for the treatment of PTSD based on the available data presented. Although data from three clinical studies were submitted, the FDA stated in the CRL that not all of these studies are capable of contributing to the substantial evidence of the submission and should Otsuka and Lundbeck be interested in proceeding with the indication, additional positive, adequate and well-controlled trials would be needed to provide substantial evidence of effectiveness.

"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," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. "Otsuka and Lundbeck will take time to review the contents of the letter with the FDA to determine the appropriate path forward."

Johan Lutham, executive vice president of Lundbeck Research & Development, commented, "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 and commitment to advancing care for those living with PTSD."

About Brexpiprazole

Brexpiprazole was approved in the U.S. by FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Most recently, brexpiprazole was approved in the U.S. for the treatment of agitation associated with dementia due to Alzheimer's disease, in May 2023. Brexpiprazole has also been approved in more than 60 countries worldwide, including the European Union, Canada and Japan.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown. Brexpiprazole has high receptor binding affinity to norepinephrine, serotonin and dopamine receptors. It is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT_2A receptors, as well as a partial agonist at serotonin 5-HT_1A and dopamine D2 receptors.