Axsome Therapeutics not too long ago introduced they’ve submitted a supplemental NDA (sNDA) to the US Meals and Drug Administration (FDA) for dextromethorphan-bupropion (AXS-05) for the remedy of Alzheimer illness agitation.1
“Our broad improvement pipeline continues to advance, and we not too long ago submitted our supplemental NDA for AXS-05 for the remedy of Alzheimer illness agitation, a critical situation affecting hundreds of thousands of sufferers within the US, and a important unmet medical want,” stated Herriot Tabuteau, MD, Chief Govt Officer of Axsome Therapeutics. “With strong business efficiency and pipeline execution, Axsome is properly positioned to proceed delivering substantial and sustained development and transformative new medicines for sufferers dwelling with critical CNS issues.”
AXS-05 is Axsome’s novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor being developed for the remedy of Alzheimer illness agitation and smoking cessation. AXS-05 was granted FDA Breakthrough Remedy designation for Alzheimer illness agitation again in 2020,the second Breakthrough Remedy designation granted to Axsome for AXS-05 (the primary being for main depressive dysfunction).2
The Breakthrough Remedy designation for AXS-05 in Alzheimer illness agitation was supported by the constructive outcomes from the pivotal section 2/3 ADVANCE-1 examine, a randomized, double-blind, managed, multicenter US trial. Investigators handled 366 members with Alzheimer illness with AXS-05, bupropion, or placebo. On this trial, remedy with AXS-05 resulted in a speedy, substantial, and statistically vital enchancment in agitation as in contrast with placebo. On the first endpoint, AXS-05 demonstrated a statistically vital imply discount from baseline within the Cohen Mansfield Agitation Stock (CMAI) complete rating in comparison with placebo at week 5, with imply reductions of 15.4 factors for AXS-05 and 11.5 factors for placebo (P=0.010). AXS-05 was additionally superior to bupropion on the CMAI complete rating (P <0.001), establishing element contribution. AXS-05 was additionally properly tolerated and never related to cognitive impairment or sedation. Essentially the most generally reported hostile occasions within the AXS-05 arm have been somnolence (8.2% for AXS-05 vs 4.1% for bupropion and three.2% for placebo), dizziness (6.3%, 10.2%, 3.2%, respectively), and diarrhea (4.4%, 6.1%, 4.4%, respectively).2
Axsome additionally intends to provoke a pivotal section 2/3 trial of AXS-05 in smoking cessation in late 2025. In response to analysis, AXS-05 considerably diminished every day smoking when put next with bupropion, with a 25% better lower within the common variety of cigarettes smoked every day over a 3-week interval. Sufferers receiving AXS-05 had a mean discount of 8.49 cigarettes per day, in contrast with a 6.79 discount for sufferers receiving bupropion. Moreover, sufferers receiving AXS-05 confirmed a greater than 50% discount in expired carbon monoxide ranges, a biochemical marker of smoking depth, in contrast with a 30.4% discount for sufferers receiving bupropion.3
References
1. Axsome Therapeutics studies third quarter 2025 monetary outcomes and supplies enterprise replace. Information launch. November 3, 2025. Accessed November 4, 2025.
2. Axsome Therapeutics receives FDA breakthrough remedy designation for AXS-05 for the remedy of Alzheimer’s illness agitation. Information launch. June 26, 2020. Accessed November 4, 2025.
3. Axsome’s AXS-05 helps sufferers stop smoking considerably in section II trial. Information launch. April 16, 2019. Accessed November 4, 2025.