About seven out of ten cases of Alzheimer’s are accompanied by symptoms of agitation and aggression. This could mean pacing, restlessness, shouting and screaming, even pushing or hitting. These behaviors—often triggered by stressful disruptions in daily life, like lack of sleep, a change in routine, other emotional distress—make an already-challenging journey all the more challenging. Now, a new drug for agitation in Alzheimer’s is making progress.
Previous research has shown that there a number of things that may help mitigate agitation and aggression for people living with Alzheimer’s, from regular exercise, to personalized music to pets. Cases have also been made that non-drug treatments for aggression and agitation may be more effective than the existing pharmaceutical options. But for more severe symptoms, there is a dire need for effective drug development:
In a March paper published in International Psychogeriatrics, scientists determined that often, people with dementia living in aged-care facilities experiencing these symptoms are using antipsychotics, “for too long, for off-label indications and without documented consent.” Antipsychotics may also come with an increased risk of mortality in older people living with dementia. A possible answer from Axsome Therapeutics is moving ahead in trials, according to the drugmaker’s announcement this week.
The experimental drug, AXS-05, is a combination of two well-known drugs: dextromethorphan, a serotonin inhibitor, and bupropion, a nicotine inhibitor. The combined drugs have previously shown promise in treating Major Depressive Disorder.
According to Axsome, a Phase II/III trial for AXS-05 hit the primary endpoints (the endpoint for which the subjects are randomized). Researchers are preparing to move ahead to the next stage of testing the drug’s effectivity.
“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,” said Jeffrey Cumming, 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.
According to Cumming, trials found a “clinically significant” reduction in agitation for test subjects, and the safety and tolerance of the drug were favorable.
“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,” Cumming said “Given the lack of approved treatments for Alzheimer’s disease agitation, 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 toward urgently needed treatment for this serious complication of Alzheimer’s disease.”
The trial involved 366 participants diagnosed with Alzheimer’s disease, randomly assigned to receive AXS-05, a placebo, or bupropion, an antidepressant, in a 1:1:1 ratio. After five weeks, the participants assessed on the Cohen Mansfield Agitation Inventory, a 29-item scale to measure agitation. AXS-05 brought about a significant improvement, according to the researchers, superior to the placebo and antidepressant.
According to reporting by Evaluate, Axsome will need to carry out a second trial before they can file for approval with the FDA — a difficult milestone to pass. But the drugmaker hopes to file for approval in 2020.