Axsome Therapeutics secures FDA approval for Auvelity to treat agitation in Alzheimer’s disease, supported by Phase 3 data showing reduced symptoms and delayed relapse.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Axsome Therapeutics has received approval from the U.S. Food and Drug Administration for Auvelity (dextromethorphan HBr and bupropion HCl) for the treatment of agitation associated with dementia due to Alzheimer’s disease.
Auvelity becomes the first approved therapy specifically targeting this indication, addressing a significant unmet need. Agitation affects up to 76% of patients with Alzheimer’s disease and is associated with increased caregiver burden, faster cognitive decline, and higher rates of institutionalization.
Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, stated that the approval marks a meaningful milestone for patients and caregivers by introducing a novel, FDA-approved treatment with a distinct mechanism of action. He also noted that the therapy’s Breakthrough Therapy designation and Priority Review underscore its clinical importance and Axsome’s commitment to advancing neuroscience innovation.
The approval is supported by results from the Phase 3 ADVANCE-1 (NCT03226522) and ACCORD-2 (NCT04947553) studies. In the 5-week ADVANCE-1 trial, Auvelity demonstrated statistically significant improvement in agitation symptoms compared with placebo, as measured by the Cohen-Mansfield Agitation Inventory (CMAI). A greater proportion of patients also showed clinical improvement on the mADCS-CGIC scale.
In the long-term ACCORD-2 randomized withdrawal study, patients who continued Auvelity experienced a significantly longer time to relapse of agitation symptoms compared with those switched to placebo.
Auvelity demonstrated a favorable safety and tolerability profile across studies. The most common adverse events were dizziness and dyspepsia, and discontinuation due to adverse events occurred in 1.3% of patients, comparable to placebo.
The therapy combines dextromethorphan, which modulates NMDA and sigma-1 receptors, with bupropion, which increases dextromethorphan exposure through CYP2D6 inhibition. The precise mechanism underlying its effect in Alzheimer’s agitation is not fully understood.
George Grossberg, MD, Professor and Director of the Division of Geriatric Psychiatry at Saint Louis University School of Medicine, emphasized that agitation in Alzheimer’s dementia is a serious and burdensome condition. He noted that Auvelity demonstrated durable efficacy with significantly delayed relapse and a favorable safety profile, positioning it as an important new treatment option.
Jeffrey Cummings, MD, ScD, Chambers-Grundy Professor of Brain Sciences said agitation is a common and burdensome aspect of Alzheimer’s disease, linked to faster decline, institutionalization, and higher mortality. He added that Auvelity’s approval addresses a critical unmet need and could play an important role in managing this challenging symptom.
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About the Writer
Nikita Jha, BPharm a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.