Axsome reports positive phase 3 Alzheimer's trial results

Axsome Therapeutics has recently concluded a significant clinical program focused on AXS-05 (dextromethorphan-bupropion), a prospective treatment for agitation in Alzheimer's disease (AD). The company aims to file a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) for this oral medication by the end of the year.

Alzheimer's disease is the most prevalent form of dementia, affecting around seven million individuals in the United States. This neurodegenerative disorder gradually impairs memory and cognitive abilities, eventually hindering basic daily tasks. Agitation, marked by emotional turmoil and aggressive behavior, affects up to 70% of AD sufferers and is linked to rapid cognitive decline.

Axsome's recent update on AXS-05 detailed successful outcomes from the phase 3 ACCORD-2 trial involving 295 participants. The trial met its primary endpoint, demonstrating a statistically significant delay in the recurrence of agitation as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, when compared to a placebo. Moreover, AXS-05 fulfilled the trial's key secondary endpoint by preventing relapse and was shown to mitigate the overall severity of AD compared to placebo.

Despite these positive results, the late-stage ADVANCE-2 trial, involving 408 Alzheimer’s patients, did not achieve statistical significance for its primary endpoint, which was the change in the CMAI total score from baseline to week five. Nonetheless, Axsome reported that the results for both the primary and nearly all secondary endpoints numerically favored AXS-05 over placebo.

During these studies, AXS-05 was found to be safe and well-tolerated. It did not lead to an increased risk of falls, cognitive deterioration, or sedation in either the controlled studies or the long-term safety trials where patients were treated for six to twelve months.

Herriot Tabuteau, CEO of Axsome Therapeutics, commented on the findings, stating, "The strong results from the ACCORD-2 trial demonstrate substantial and statistically significant improvements in AD agitation with AXS-05 across three pivotal, phase 3, placebo-controlled trials—ADVANCE-1, ACCORD-1, and ACCORD-2. This underscores the drug's potential to offer meaningful benefits to patients struggling with this condition and their families."

While the improvements in the AXS-05 group compared to placebo in ADVANCE-2 did not achieve statistical significance, Tabuteau expressed satisfaction with the robust safety data from this trial. This information will play a crucial role in the company's planned NDA submission targeted for the second half of 2025.

The promising outcomes from the ACCORD-2 trial, coupled with the safety profile observed across the studies, suggest that AXS-05 could become a valuable treatment option for managing agitation in Alzheimer's patients. With the condition being a significant challenge for millions of individuals and their caregivers, AXS-05 holds the potential to alleviate some of the burdens associated with this aspect of Alzheimer's disease. Axsome Therapeutics is eager to move forward with the regulatory process, aiming to offer a new therapeutic option for those affected by Alzheimer's-related agitation.