Axsome Therapeutics' investigational oral therapy AXS-05 significantly and rapidly lessened agitation in patients with Alzheimer’s disease, top-line results from a Phase 2/3 trial show. The therapy also was found to be generally well-tolerated and safe, without affecting cognition. “I am very pleased to see the promising results of the ADVANCE-1 trial, providing clear evidence of reduced agitation in Alzheimer’s disease by this investigational medicine,” Jeffrey Cummings, MD, ScD, director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Chambers professor of brain science at the University of Nevada Las Vegas, said in a press release. AXS-05 aims to treat agitation — an umbrella term that refers to feelings of restlessness, emotional distress, aggression, irritability, and a loss of social awareness — in people with Alzheimer’s. Currently, no treatments are approved for this frequent disease complication. “Agitation occurs in the majority of patients with Alzheimer’s disease, is very distressing to patients and their families, and is associated with greater risk of institutionalization and accelerated progression to severe dementia and death,” Cummings said. “Given the lack of approved treatments ... and the safety concerns and modest or uncertain efficacy of currently used off-label treatments, the AXS-05 study results represent a meaningful step forward.” AXS-05 has two main active components, dextromethorphan and bupropion. Dextromethorphan works by modulating the activity of neurotransmitters (chemicals used to send signals between nerve cells), including glutamate, serotonin, and norepinephrine, which have been linked to cognitive and behavioral changes in people with Alzheimer’s disease.