The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for AXS-05 (dextromethorphan HBr and bupropion HCl) as a treatment for Alzheimer disease agitation.
AXS-05 consists of dextromethorphan, an uncompetitive N-methyl D-aspartate receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor. The combination therapy was previously approved for the treatment of major depressive disorder under the brand name Auvelity®.
The sNDA for Alzheimer disease agitation is supported by 4 randomized, double-blind, phase 3 trials: ADVANCE-1 (ClinicalTrials.gov Identifier: NCT03226522), ADVANCE-2 (ClinicalTrials.gov Identifier: NCT05557409), ACCORD-1 (ClinicalTrials.gov Identifier: NCT04797715) and ACCORD-2 (ClinicalTrials.gov Identifier: NCT04947553). Long-term safety was also assessed in an open-label extension trial (ClinicalTrials.gov Identifier: NCT06736509).
Findings from these studies showed AXS-05 improved agitation-related and disruptive behaviors and delayed the time to relapse of Alzheimer disease agitation compared with placebo. The ADVANCE-2 trial did not meet statistical significance for its primary endpoint (change in the Cohen-Mansfield Agitation Inventory total score from baseline to week 5), though numerically more favorable results were observed with AXS-05 than placebo. Safety data through 12 months showed the treatment was well tolerated.
“We are very pleased the FDA has accepted and granted priority review to our supplemental NDA for AXS-05 for the treatment of Alzheimer disease agitation,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Up to 76% of people with Alzheimer disease experience agitation, representing a significant unmet medical need for patients and their caregivers, and currently there is a dearth of approved treatments. We look forward to continuing to work with the FDA for the remainder of the review.”
A Prescription Drug User Fee Act date of April 30, 2026 has been assigned to the application.
References:
Axsome Therapeutics announces FDA acceptance and Priority Review of supplemental New Drug Application for AXS-05 for the treatment of Alzheimer’s disease agitation. News release. Axsome Therapeutics. December 31, 2025. https://www.globenewswire.com/news-release/2025/12/31/3211743/33090/en/Axsome-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-Supplemental-New-Drug-Application-for-AXS-05-for-the-Treatment-of-Alzheimer-s-Disease-Agitation.html.
