The US Food and Drug Administration has accepted Axsome Therapeutics’ supplemental New Drug Application (sNDA) for AXS-05 for the treatment of agitation associated with Alzheimer’s disease and has granted the application Priority Review status.
The agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2026. AXS-05 is an oral, extended-release combination therapy comprising dextromethorphan hydrobromide and bupropion hydrochloride. The drug acts as an NMDA receptor antagonist, sigma-1 receptor agonist, and aminoketone CYP2D6 inhibitor, using a proprietary formulation and dosing regimen.
An extended-release tablet containing the same active ingredients—dextromethorphan HBr 45 mg and bupropion HCl 105 mg—was previously approved in 2022 under the brand name Auvelity for the treatment of major depressive disorder.
In December 2024, Axsome reported completion of its phase 3 clinical development program evaluating AXS-05 for Alzheimer’s disease agitation. Three of the four phase 3 trials met their primary efficacy endpoints. One study, the ADVANCE-2 phase 3 trial, did not achieve statistical significance on its primary endpoint, which measured change in the Cohen-Mansfield Agitation Inventory total score from baseline to week five. However, the company reported that both the primary and nearly all secondary endpoints in this trial numerically favored AXS-05 over placebo, supporting the decision to proceed with the sNDA submission.
If approved, AXS-05 could offer a new oral treatment option for agitation in patients with Alzheimer’s disease, an area with significant unmet medical need.
