Axsome Therapeutics announced the completion of its phase 3 clinical program evaluating its oral, investigational NMDA receptor antagonist, sigma-1 agonist and aminoketone CYP2D6 inhibitor in Alzheimer’s disease agitation, with three out of the four trials hitting their primary endpoints.
The ACCORD-2 phase 3 trial achieved its primary endpoint with AXS-05 (dextromethorphan-bupropion) delaying the time to relapse of agitation, assessed by the Cohen-Mansfield Agitation Inventory (CMAI) total score, in patients with Alzheimer’s disease compared to placebo.
The New York-based biopharma has previously reported statistically significant efficacy compared to placebo in two other pivotal phase 3 trials — ADVANCE-1 and ACCORD-1.
However, the ADVANCE-2 phase 3 trial did not demonstrate statistical significance for the primary endpoint — change in the 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.
Given the results of the three successful trials and long-term safety trials in the indication, Axsome plans to submit an NDA for AXS-05 in Alzheimer’s disease agitation to the FDA in the second half of 2025.
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.