Results from a phase 3 trial evaluating AXS-05 in patients with Alzheimer disease agitation showed that the investigational oral therapy significantly delayed and reduced symptom relapse.
AXS-05 consists of dextromethorphan, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, and bupropion, a norepinephrine and dopamine reuptake inhibitor that serves to increase the bioavailability of dextromethorphan.
The double-blind, placebo-controlled, randomized ACCORD study (ClinicalTrials.gov Identifier: NCT04797715) included patients with a diagnosis of probable Alzheimer disease and clinically meaningful agitation associated with the disease. The study included a 9-week, open-label period in which patients were treated with AXS-05. During the open-label treatment period, statistically significant improvements on the Cohen-Mansfield Agitation Inventory (CMAI) were observed at all timepoints starting at week 1 (P <.001). Significant improvements in caregiver distress and burden, patient quality of life, and depressive symptoms were also observed after treatment with AXS-05.
A total of 108 patients achieved a sustained clinical response during the open-label period and were randomly assigned to continue receiving treatment with AXS-05 (n=53) or switch to placebo (n=55) for up to 26 weeks. Findings from the double-blind period showed that treatment with AXS-05 substantially and statistically significantly delayed the time to relapse of Alzheimer disease agitation (primary endpoint) compared with placebo (hazard ratio [HR] for time to relapse of 0.275; P =.014).
AXS-05 also significantly prevented relapse of Alzheimer disease agitation (secondary endpoint), with 7.5% of patients treated with AXS-05 relapsing vs 25.9% of patients treated with placebo (P =.018). Relapse was defined as at least a 10-point worsening in the CMAI total score from randomization or at study entry; or hospitalization or other institutionalization due to agitation associated with Alzheimer disease. The rates of adverse events were 28.3% in the AXS-05 arm and 22.2% in the placebo arm. Discontinuation due to adverse events was reported to be 0% in the AXS-05 arm and 1.9% in the placebo arm.
“The ACCORD results complement, and are consistent with, those from the previously completed positive ADVANCE-1 trial,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “We intend to discuss these findings with the FDA in the context of the ongoing clinical development of AXS-05 in this indication, with the goal of providing a much needed treatment to the millions of patients living with Alzheimer’s disease agitation and their caregivers.”
The FDA previously granted Breakthrough Therapy designation to AXS-05 for this indication.
Axsome Therapeutics announces AXS-05 achieves primary endpoint in the ACCORD phase 3 trial in Alzheimer’s disease agitation. News release. Axsome Therapeutics, Inc. Accessed November 28, 2022. https://www.globenewswire.com/news-release/2022/11/28/2562961/33090/en/Axsome-Therapeutics-Announces-AXS-05-Achieves-Primary-Endpoint-in-the-ACCORD-Phase-3-Trial-in-Alzheimer-s-Disease-Agitation.html