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FDA denies approval for Rexulti in PTSD treatment, citing insufficient evidence despite clinical trials. Otsuka and Lundbeck plan next steps.
The CRL states the FDA completed its review but cannot approve the treatment in its current form.
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Lundbeck and Otsuka America Pharmaceutical announced Otsuka has received a Complete Response Letter (CRL) from FDA regarding the supplemental New Drug Application (sNDA) for use of Rexulti in combination with sertraline as a treatment of adults with post-traumatic stress disorder (PTSD). The CRL includes FDA’s completed review, along with its decision to not approve Rexulti, stating that the application does not provide substantial evidence of effectiveness to support the approval.1
FDA accepted Rexulti for review back in June 2024 for the treatment of PTSD in adults, which was based on data from three randomized clinical trials evaluating Rexulti’s safety and efficiency in combination with sertraline in adults’ patients with PTSD.
FDA’s decision on Rexulti follows the Psychopharmacologic Drugs Advisory Committee Meeting back on July 18 of this year, where the committee voted 1-10 determining that the treatment’s efficiency when initiated simultaneously with sertraline is not established to treat PTSD based on available data presented to the committee.1 Despite data from three clinical studies being submitted, FDA stated in the CRL that none of the studies are capable of contributing substantial evidence to the submission, and continued to add that if Otsuka and Lundbeck seek to continue proceeding with the indication, additional positive, adequate, and well-controlled trials would be needed to provide substantial evidence of effectiveness.1
“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.”
Rexulti (Brexpiprazole) received approval in the U.S. by FDA back in 2015 as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD), and as a treatment for schizophrenia in adults, along with being approved in the U.S. as a treatment for agitation associated with dementia due to Alzheimer's disease. Rexulti is approved across 60 countries worldwide, including approvals in the European Union, Canada, and Japan.1 Discovered by Otsuka, Rexulti is being co-developed by Otsuka and Lundbeck, and its mechanism of action is currently unknown. Rexulti holds a high receptor binding affinity to norepinephrine, serotonin and dopamine receptors, and is an antagonist to norepinephrine α1B and α2C receptors and serotonin 5-HT2A receptors, along with being a partial agonist to serotonin 5-HT1A and dopamine D2 receptors.1
Johan Luthman, executive vice president of Lundbeck Research & Development, commented following reception of the CRL, saying, “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.”
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