Latest Findings on AXS-05 Treatment for Agitation in Alzheimer Disease: Anton P. Porsteinsson, MD

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"The primary outcome measure, time to relapse, showed a statistically significant superiority for those continuing on AXS-05 treatment, with a 3 times lower risk of relapse than those on placebo."

ACCORD (NCT04797715) is a phase 3, double-blind, multi-center, randomized-controlled trial that assessed the efficacy and safety of AXS-05 (Axsome Therapeutics), an oral NMDA receptor antagonist/sigma-1 receptor agonist that is FDA-approved for major depressive disorder, in patients with Alzheimer disease (AD) associated agitation. In the 9-week, open-label period (OLP) participants enrolled were treated with AXS-05 (n = 178) and responders (n = 108) were randomized. Those who discontinued were the ones who had a relapse of agitation reported. The primary and key secondary end points included time from randomization to relapse of agitation symptoms and rates of agitation relapse.

Recent findings from the trial showed that AXS-05 significantly reduced the risk of agitation symptom relapse in patients with AD. Among those enrolled in the OLP, AXS-05 treatment resulted in statistically significant improvement from baseline in Mansfield Cohen Agitation Index (CMAI) scores at all timepoints from week 1 (6.7 points; P <.001) to week 5 (20.6 points; P <.001). Notably, AXS-05 met the primary end point by delaying the time to relapse of agitation symptoms as compared with placebo (HR = 0.276; P =.014) in the 26-week double-blind period with responders. Additionally, AXS-05 met the key secondary end point of improved relapse prevention (7.5%) compared with placebo (25.9%, P = .018).

Anton P. Porsteinsson, MD, director of the Alzheimer's Disease Care, Research and Education Program at University of Rochester, presented these findings at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado. Porsteinsson, who also serves as the William B. and Sheila Konar Professor of Psychiatry at University of Rochester School of Medicine and Dentistry, sat down with NeurologyLive^® after the meeting for an interview to dive deeper into the results of ACCORD. He also further discussed the structure of the study and the criteria used for patient selection. In addition, Porsteinsson shared some of the safety considerations and adverse events observed in the study.

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REFERENCES
1. Cummings J, Grossberg G, Andersson C, Streicher C, and Tabuteau H. Efficacy and Safety of AXS-05 in Agitation Associated with Alzheimer’s Disease: Results from ACCORD, a Phase 3, Double-blind, Placebo-controlled, Relapse Prevention Trial. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. Clinical Trials Plenary Session.