Experimental Combo Treatment Reduced Alzheimer Disease-Associated Agitation

Results of the ACCORD (NCT04797715) clinical trial presented at the 2024 meeting of the Alzheimer’s Association International Conference (AAIC) demonstrated that AXS-05 (dextromethorphan-bupropion; Axsome Therapeutics, New York, NY) treatment reduced agitation symptom relapse and was well-tolerated in participants with Alzheimer disease (AD)-associated agitation. AXS-05, an NMDA receptor antagonist and sigma-1 receptor agonist, is Food and Drug Administration (FDA)-approved for major depressive disorder.

The multi-center phase 3 trial consisted of a 9-week open-label period (OLP) followed by a 26-week double-blind period (DBP) for responders (defined as participants with ≥30% improvement from baseline in the Cohen Mansfield Agitation Inventory [CMAI] total score and Patient Global Impression of Change [PGI-C] score improvements ≤3 lasting ≥4 consecutive weeks) who were randomized to receive ether AXS-05 (n=53) or placebo (n=55). The primary endpoint was time to relapse of agitation symptoms and the key secondary endpoint was rate of agitation relapse.

• Participants receiving AXS-05 treatment during the OLP (n=178) showed a significant improvement from baseline in CMAI scores at all time points from week 1 (6.7 points, P<.001) to week 5 (20.6 points, P<.001).
• There was a 3.6-fold lower risk of relapse of agitation symptoms in responders treated with AXS-05 compared with placebo (hazard ratio [HR]=0.276, P=.014).
• Relapse rates were significantly lower in responders treated with AXS-05 (7.5%) compared to placebo (25.9%, P=.018).
• Adverse event rates were comparable between AXS-05 (28.3%) and placebo (22.2%).
• There was no evidence of cognitive decline or sedation with AXS-05 treatment.