FDA Approves First Pharmacological Treatment for Dementia-Related Agitation

The US Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) of REXULTI® (brexpiprazole) for the treatment of agitation associated with dementia related to Alzheimer disease. This approval marks REXULTI® as the first and only pharmacological treatment approved in the US for this condition. Otsuka Pharmaceutical and Lundbeck LLC announced the sNDA approval late Wednesday.

“Today marks a major milestone for patients, caregivers, and families navigating the complexities of agitation associated with dementia due to Alzheimer disease,” Makoto Inoue, president and representative director of Otsuka, expressed in a news release. “Otsuka Pharmaceutical will continue its efforts to engage and provide options for those impacted by this devastating condition,” 

The sNDA for brexpiprazole received priority review from the FDA, indicating the drug’s recognition as a significant improvement in the treatment of a serious medical condition. The submission was based on two Phase 3 studies that evaluated the frequency of agitation symptoms in patients with dementia due to Alzheimer disease. The primary endpoint in both studies was the change in agitation symptom frequency from baseline at Week 12.

Patients treated with brexpiprazole achieved a 31% greater reduction in the frequency of agitation symptoms compared to those receiving a placebo. The drug was well-tolerated, with a low incidence of discontinuations and a safety profile consistent with its known profile in other indications.

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The mechanism of action of brexpiprazole is not fully understood, but it is believed to involve a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, along with antagonist activity at serotonin 5-HT2A receptors.

Brexpiprazole is not indicated as an as-needed treatment for agitation associated with dementia due to Alzheimer disease.

Brexpiprazole, discovered by Otsuka and co-developed by Otsuka and Lundbeck, was initially approved in the US in 2015 for major depressive disorder (MDD) and schizophrenia. It has also received approvals for schizophrenia and adjunctive treatment of MDD in other countries. 

Brexpiprazole carries important safety information, including an increased risk of death in elderly people with dementia-related psychosis and an increased risk of suicidal thoughts and actions, especially in individuals under 24 years of age. The listed information urges patients and caregivers to remain vigilant for any changes in mood, behavior, thoughts, or feelings, and to report them to the doctor immediately.

Reference

Otsuka and Lundbeck announce US Food and Drug Administration (FDA) approval of supplemental new drug application (sNDA) for REXULTI® (brexpiprazole) for the treatment of agitation associated with dementia due to Alzheimer’s disease. News release. Otsuka. May 10, 2023. Accessed May 11, 2023. https://otsuka-us.com/news/otsuka-and-lundbeck-announce-us-food-and-drug-administration-fda-approval-supplemental-new