AXS-05 is a medication being developed by Axsome Therapeutics for the treatment of agitation in people with Alzheimer’s disease. The oral medication combines two compounds: bupropion and dextromethorphan.

The U.S. Food and Drug Administration (FDA) granted AXS-05 breakthrough therapy designation in June 2020 to help expedite its development and approval. That designation is awarded to an investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement over available therapies.

The treatment had received the FDA’s fast track designation in May 2017. Fast Track status provides greater access to, and more frequent communication with, the FDA throughout the entire drug development and review process. Its goal is to get new medications to patients more rapidly.

How does AXS-05 work?

Dextromethorphan, the first component of AXS-05, is commonly used as a cough suppressant. The medicine has potent effects on various neurotransmitter systems in the brain — comprising the body’s chemical messengers — that may be involved in agitation. These include glutamateserotonin, and norepinephrine. However, the body breaks down dextromethorphan very quickly, which can limit its effectiveness.

The second component of AXS-05, bupropion, stabilizes dextromethorphan to make it more effective. In addition, bupropion increases the availability of the neurotransmitters dopamine and norepinephrine, and acts on acetylcholine, which also may play a role in agitation. 

Agitation is an umbrella term that refers to feelings of restlessness, emotional distress, aggression, irritability, and a loss of social awareness. It is reported in about 50% of Alzheimer’s patients.

AXS-05 in clinical trials

Axsome began a Phase 2/3 clinical trial (NCT03226522) in the summer of 2017 to investigate the safety and effectiveness of AXS-05 in treating agitation in people with Alzheimer’s. Participants were randomly assigned to receive either AXS-05 (159 people), bupropion only (49 people), or a placebo (158 people), for five weeks. The researchers assessed patients’ agitation symptoms using the Cohen-Mansfield agitation inventory (CMAI.)

Following a pre-planned interim analysis in late 2018, however, enrollment in the bupropion arm ceased; the researchers randomly assigned those subsequently entering the study to either AXS-05 or a placebo.

The trial, expected to conclude in in June 2020, was completed early due to concerns related to the COVID-19 pandemic. Top-line results demonstrated that, at week five, patients in the AXS-05 group showed a significant reduction in CMAI scores compared with the placebo or bupropion groups. The therapy also was found to be generally well-tolerated and safe, without affecting cognition.


Last updated: June 30, 2020


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