FDA approves first-in-class Auvelity for agitation in Alzheimer’s disease

The FDA has approved Axsome Therapeutics’ Auvelity (dextromethorphan–bupropion) as a first-in-class treatment for agitation in Alzheimer’s disease, targeting NMDA and sigma-1 receptors. Agitation affects up to about 70% of patients and worsens caregiver burden and mortality. In phase 3 trials ACCORD-2 and ADVANCE-2, Auvelity delayed relapse of agitation compared with placebo (ACCORD-2: hazard ratio 0.275, P=0.001; relapse 8.4% vs 28.6%). ADVANCE-2 did not meet its primary CMAI endpoint but showed numerical improvements. Auvelity had FDA Breakthrough Therapy designation and an sNDA was submitted in 2025. Experts say this provides a meaningful new option with a favorable safety profile, potentially easing patient and caregiver burden.