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Axsome Launches AXS-05 Phase 3 Trial for Alzheimer’s-associated Agitation

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Aduhelm and FDA label change


Axsome Therapeutics has launched a Phase 3 trial that will assess the safety and efficacy of AXS-05, the company’s investigational oral treatment for agitation associated with Alzheimer’s disease.

If positive, data from the trial is expected to support Axsome’s submission of an application requesting the therapy’s approval for treating Alzheimer’s patients with agitation. According to the company, top-line data from the study, called ACCORD, is expected in 2022.

“Initiation of the ACCORD Phase 3 trial in Alzheimer’s disease agitation continues the expedited clinical development of AXS-05 for this serious condition,” Herriot Tabuteau, MD, CEO of Axsome, said in a press release.

“Alzheimer’s disease agitation is a prevalent and debilitating condition that is associated with earlier nursing home placement, accelerated progression to severe dementia, and increased risk of death,” Tabuteau said, noting that there currently are no approved treatments for this problem.

“If successfully developed, AXS-05 has the potential to address this high unmet need and significantly improve the lives of patients and their caregivers,” Tabuteau said.

AXS-05 is based on a proprietary formulation of two active ingredients, dextromethorphan and bupropion. Dextromethorphan is able to control the activity of multiple neural signals that are thought to influence the cognition and behavior of people with Alzheimer’s. Bupropion, in turn, also regulates the activity of these neural chemicals, and is thought to increase the stability and effectiveness of dextromethorphan.

The therapy’s safety and efficacy in patients with agitation associated with Alzheimer’s were previously investigated in a recently completed Phase 2/3 trial, called ADVANCE-1 (NCT03226522). Top-line data from ADVANCE-1 showed AXS-05 was safe, and significantly and rapidly lessened agitation in Alzheimer’s patients.

These promising results led the U.S. Food and Drug Administration (FDA) to grant AXS-05 the designation of breakthrough therapy. This designation is given to accelerate the development and review of promising experimental therapies aiming to treat serious or life-threatening conditions.

Axsome had a meeting with the U.S. regulatory agency shortly after the announcement of the new designation to discuss AXS-05’s future development. During the meeting, the FDA confirmed the pivotal status of ADVANCE-1 and stated that favorable results from a second pivotal placebo-controlled trial would likely be sufficient to support AXS-05’s approval as a therapy to ease agitation associated with Alzheimer’s.

Following the FDA’s recommendation, Axsome has now launched ACCORD, the second pivotal study that is expected to support the therapy’s future approval.

ACCORD will follow a randomized-withdrawal design, in which patients will first complete a nine-week open-label treatment course in which everyone receives AXS-05. Those responding to the treatment will then be randomly assigned to either continue receiving AXS-05 or switch to a placebo, for up to 26 weeks (about six months) or until experiencing an episode of agitation.

The study’s main goal will be to assess the effects of treatment on the time it takes for patients to experience a relapse of agitation following their randomized selection for differing treatments. Additional study goals will include evaluating the therapy’s safety, as well as its effects on patients’ agitation levels, which will be determined based on their scores on the Cohen-Mansfield Agitation Inventory (CMAI).

Patients completing ACCORD will then have the chance to continue treatment with AXS-05 by enrolling in the study’s open-label safety extension trial, which is expected to launch soon.

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