The Food and Drug Administration’s (FDA) Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee voted 9 to 1 in favor of the use of brexpiprazole (Rexulti®) for the treatment of agitation associated with Alzheimer dementia (AAD). The majority of the panel believed that the data provided were sufficient to allow for the identification of a population in whom the benefits of treating AAD with brexpiprazole outweighed the potential risks associated with use of atypical antipsychotics.
The FDA panel reviewed data from three 12-week, double-blind, placebo-controlled phase 3 studies (Study 331-12-283 [ClinicalTrials.gov Identifier: NCT01862640], Study 331-12-284 [ClinicalTrials.gov Identifier: NCT01922258], and Study 331-14-213 [ClinicaTrials.gov Identifier: NCT03548584]) in which patients with AAD were randomly assigned to receive either brexpiprazole or placebo. The primary endpoint for both studies was the change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score at week 12.
In Study 331-12-283, results showed that treatment with brexpiprazole 2mg/day significantly improved symptoms of agitation compared with placebo (P <.05) based on the mean change in CMAI total score from baseline to week 12. A statistically significant improvement was also observed with brexpiprazole 2mg/day and 3mg/day compared with placebo (P <.05) in Study 331-14-213. However, the primary endpoint was not met in Study 331-12-284.
An assessment of mortality risk across clinical trials showed that the effect of brexpiprazole appeared to be consistent with the risk associated with other antipsychotics used in elderly patients with dementia. Treatment emergent adverse events that occurred in at least 2% of brexpiprazole-treated patients and more than with placebo were insomnia, somnolence, nasopharyngitis, and urinary tract infection.
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. A Prescription Drug User Fee Act target date of May 10, 2023 has been set for the application. If approved, brexpiprazole would be the first medication indicated for AAD in the US.
- Otsuka and Lundbeck issue statement on US Food and Drug Administration (FDA) advisory committee meeting on Rexulti® (brexpiprazole) for the treatment of agitation associated with Alzheimer’s dementia. News release. Otsuka and Lundbeck. April 16, 2023. https://www.newsroom.lundbeckus.com/news-release/2023/otsuka-and-lundbeck-issue-statement-on-u-s–food-and-drug-admini.
- FDA Briefing Document. Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee. April 14, 2023. https://www.fda.gov/media/167066/download.