Novel receptor agonist linked to significant improvement in Alzheimer’s-related agitation

Key takeaways:

• Treatment with AXS-05 in the open-label period resulted in rapid and meaningful improvements in agitation.
• The risk of relapse of agitation was 3.6 times lower for those given AXS-05 compared with placebo.

DENVER — Treatment with a novel, oral receptor agonist led to rapid and significant improvements in those with agitation related to Alzheimer’s disease, according to a speaker at the American Academy of Neurology annual meeting.

“Alzheimer’s disease related agitation is reported in about 70% of patients at some stage of their disease course,” Anton P. Porsteinsson, MD, director of the Alzheimer’s disease care, research and education program at the University of Rochester School of Medicine and Dentistry, said during his presentation. “When you are dealing with agitation associated with AD, the first line of treatment should always be non-pharmacological, but they are not always effective.”

Porsteinsson and colleagues conducted the ACCORD study, a phase 3, double-blind, placebo-controlled trial that sought to examine safety and efficacy of AXS-05, a novel, oral, N-methyl-D-aspartate (NMDA) receptor agonist. They included 178 individuals with agitation related to AD (mean age 74.9 years; 53.4 female) in the study’s open-label period and a subset of 108 individuals randomized 1:1 to receive either AXS-05 (n = 53; mean age 74.1 years; 50.9% female) or placebo (n = 55; mean age 74.9 years; 54.5% female).

Following a screening period of roughly 4 weeks, an open-label period in which AXS-05 was given twice a day lasted up to 9 weeks. After randomization, either AXS-05 or placebo was administered twice a day in a double-blind period of up to 26 weeks.

The study’s primary endpoint was time from randomization to agitation relapse, with the chief secondary endpoint the percentage of participants who relapsed.

Results at week 25 showed that AXS-05 substantially increased time to relapse compared with placebo (HR = 0.275; 95% CI, 0.091-0.836), while also significantly decreasing likelihood of agitation relapse (7.5% vs. 25.9%, respectively) at week 25.

AXS-05 was found to be safe and well-tolerated, with a minimum number of adverse or treatment-emergent adverse events (TEAEs). Three serious TEAEs were reported along with four falls in the AXS-05 treatment group.

“We saw a rapid and clinically meaningful improvement in AD-related agitation,” Porsteinsson said. “The drug was not associated with cognitive impairment or sedation.”