The U.S. FDA has accepted Axsome Therapeutics’ supplemental NDA for AXS-05 (dextromethorphan HBr and bupropion HCl) for the treatment of Alzheimer’s disease agitation, granting the application priority review designation.
The agency has set a PDUFA target action date of April 30, 2026 for the oral NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor. AXS-05 consists of a proprietary formulation and dose of dextromethorphan and bupropion.
Axsome's extended-release oral tablet containing the same ingredients — dextromethorphan HBr (45 mg) and bupropion HCl (105 mg) — was approved under the brand name Auvelity for the treatment of major depressive disorder back in 2022.
In December 2024, Axsome announced the completion of its phase 3 clinical program for AXS-05 in Alzheimer’s disease agitation, with three out of the four trials hitting their primary endpoints. The ADVANCE-2 phase 3 trial did not demonstrate statistical significance for the primary endpoint — change in the Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline to week 5. But, according to Axsome, results for the primary and nearly all secondary endpoints numerically favored AXS-05 over placebo, so the company chose to submit its sNDA despite the trail fail.