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New Drug Shows Promise for Reducing Agitation in Alzheimer Disease Patients
AXS-05 (dextromethorphan-bupropion), a novel oral n-methyl-D-aspartate (NMDA) receptor antagonist, reportedly prevents the relapse and significantly delays time to relapse of agitation in Alzheimer disease (AD) patients, according to a recent press release from manufacturer Axsome Therapeutics.
The ACCORD (Assessing Clinical Outcomes in Alzheimer Disease Agitation) Phase 3 trial tested AXS-05 in a double-blind, placebo-controlled, multi-center, randomized withdrawal study involving 178 patients with Alzheimer disease agitation to investigate the drug’s ability to delay time to relapse of symptoms over 9 weeks.
The trial met its primary endpoint by “substantially and statistically significantly delaying the time to relapse of agitation symptoms as compared to placebo.” Patients were considered to have a sustained clinical response if they exhibited at least a 30% improvement on the Cohen-Mansfield Agitation Inventory (CMAI) total score and improvement on the Patient Global Impression-Clinician (PGI-C) score of at least 3 that was maintained for at least 4 consecutive weeks. The hazard ratio for time to relapse was 0.275 (p=0.014), amounting to a risk for relapse that was 3.6 times lower than placebo.
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Those who responded to the treatment (n=108) were then randomly assigned on a 1:1 basis to continue with AXS-05 or switch to placebo to examine the drug’s effectiveness in preventing relapse of Alzheimer disease agitation. During the open-label period, patients “experienced rapid, substantial, and statistically significant improvement.” From a baseline mean CMAI score of 70.9, the mean reduction at Week 2 was 11.0 points (p<0.001) and 20.6 points at Week 5 (p<0.001).
Some adverse events were experienced at the rate of 28.3% in the AXS-05 treatment group and 22.2% in the placebo group. Discontinuation due to adverse events was low (0% for AXS-05; 1.9% for placebo). One case of serious adverse event in the AXS-05 group involved faecaloma was determined to be unrelated to treatment.
“Agitation is one of the most troubling and consequential aspects of Alzheimer’s disease for patients and their caregivers as it is associated with early nursing home placement, accelerated cognitive decline, and increased mortality.[…] Agitation occurs in the majority of patients with Alzheimer’s disease and there are currently no treatments approved for this condition,” said Jeffrey Cummings, MD, ScD, profess of Brain Science, University of Nevada, Las Vegas, of the trial results. “AXS-05 could potentially fill this high unmet medical need for patients and their caregivers, if approved, based on the observed positive efficacy and favorable safety and tolerability results.”
AXS-05 was granted Breakthrough Therapy designation for the treatment of AD agitation by the US Food and Drug Administration in June 2020.
References
Meligo M. AXS-05 meets primary end point in phase 3 trial of Alzheimer agitation. Neurology Live. Published online November 29, 2022. Accessed online December 12, 2022.
