Axsome Therapeutics secured FDA approval to expand AUVELITY (dextromethorphan HBr and bupropion HCl) use beyond depression, a first-in-class therapy targeting NMDA and sigma-1 receptors in the brain. Agitation in Alzheimer’s disease patients—ranging from restlessness to verbal and physical aggression—occurs in up to 76% of individuals with the disease, which affects more than 7 million Americans. The condition remains one of the most challenging and costly aspects of care.
AUVELITY is described as a first-in-class mechanism, with its dextromethorphan component acting on both NMDA and sigma-1 receptors. The bupropion component increases dextromethorphan exposure by inhibiting the CYP2D6 enzyme. The FDA’s decision was supported by Phase 3 trials ADVANCE-1 and ACCORD-2. In ADVANCE-1, AUVELITY demonstrated statistically significant improvement in agitation symptoms versus placebo based on the Cohen-Mansfield Agitation Inventory (CMAI) total score. A higher proportion of patients also showed clinical improvement on a key secondary measure compared with placebo. ACCORD-2, a longer-term randomized withdrawal study, found that patients who continued AUVELITY experienced a significantly longer time to relapse compared with those switched to placebo.
AUVELITY was previously approved for major depressive disorder in adults, an indication that received Breakthrough Therapy designation and Priority Review from the FDA. According to the company, the drug has been used in more than 300,000 patients across clinical and real-world settings to date. William Blair projects AUVELITY’s peak sales for the Alzheimer’s agitation indication above $2.1 billion, within management’s broader $1.5 billion to $3 billion estimate for that indication. The competitive landscape for Alzheimer’s agitation treatment remains underpenetrated, with Rexulti—the only other FDA-approved treatment—holding just 4.6% market share as of the end of 2025.
Axsome plans to develop a selective inhibitor for treating schizophrenia and Tourette syndrome, with Phase 3 trial-enabling activities for schizophrenia beginning in 2026. In February, Axsome dosed the first patient in the CLARITY Phase 3 trial of solriamfetol for major depressive disorder with excessive daytime sleepiness.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.benzinga.com/news/fda/26/05/52210170/axsome-wins-fda-nod-for-expanded-use-for-auvelity-beyond-depression