Axsome Therapeutics’ AXS-05 challenges current standard of care as promising non-antipsychotic for Alzheimer’s agitation: GlobalData

At the recently held American Academy of Neurology (AAN) 2025 annual meeting, Axsome Therapeutics presented promising data for AXS-05 (bupropion + dextromethorphan) in treating agitation associated with Alzheimer’s disease (AD). With a novel, non-antipsychotic mechanism and a favorable safety profile, AXS-05 addresses a critical unmet need in managing distressing behavioral symptoms, potentially reshaping the current treatment paradigms in a space largely reliant on off-label antipsychotic use, says GlobalData.

Pippa Salter, Managing Neurology Analyst at GlobalData, comments, “A major unmet need in the AD market is for treatments for the many secondary symptoms associated with the disease that can negatively impact the quality of life for both patient and caregiver, with agitation highlighted by the key opinion leaders (KOLs) previously interviewed by GlobalData as a particularly distressing symptom with a lack of good treatment options.”

When agitated, patients are often prescribed antipsychotic medications and sedatives off-label to alleviate behavioral issues, a practice that the FDA states can be dangerous in elderly patients. In 2023, Otsuka Pharmaceuticals’ atypical antipsychotic Rexulti (brexpiprazole) became the first FDA-approved treatment for agitation associated with AD in the US.

Salter continues, “KOLs felt that the efficacy of Rexulti was only comparable to other atypical antipsychotics and thus not providing a significant breakthrough for AD agitation treatment. The positive efficacy for AXS-05 is particularly significant therefore as if approved it would provide a novel, non-antipsychotic treatment option for AD agitation. Additionally, in the ACCORD-2 trial AXS-05 was well tolerated, and its benign safety profile, combined with physician experience with the drug for treating major depressive disorder should give AXS-05 a further competitive advantage in the AD market.”

GlobalData’s report “Alzheimer’s Disease in Major Markets, Disease Management, Epidemiology, Pipeline Assessment, Unmet Needs and Drug Forecast to 2033,” reveals that AXS-05 will generate US sales of approximately $307.3 million in the AD market in 2033.

Salter concludes, “Other products in late-stage development for AD agitation with novel mechanisms of action, including Suven Life Sciences’s 5-hydroxytryptamine receptor 6 antagonist masupirdine and BioXcel Therapeutics’ alpha 2 adrenergic receptor agonist Igalmi (dexmedetomidine), will provide competition for AXS-05. And with Axsome Therapeutics and BioXcel Therapeutics currently focusing on development in the US only, significant opportunity for targeting AD agitation will remain outside of the US.”