The ACCORD-2 trial successfully achieved its primary endpoint, with a statistically significant delay in time to relapse of agitation compared to placebo. How clinically meaningful is this delay for patients and caregivers managing Alzheimer's-related agitation?

While ACCORD-2 met its primary endpoint, ADVANCE-2 did not reach statistical significance despite numerical improvements favoring AXS-05. What factors could explain the discrepancy between these two trials, and how should the data be interpreted collectively?

AXS-05 demonstrated significant prevention of worsening in both agitation and overall Alzheimer’s disease severity. How critical is this dual benefit in positioning AXS-05 as a potential standard of care in this challenging patient population?

AXS-05 was not associated with increased risk of falls, sedation, cognitive decline, or mortality, even in long-term use. How does this safety profile compare to current treatment options, and how important is it for regulatory approval?

Given the Breakthrough Therapy designation and the planned NDA submission in the second half of 2025, what are the key challenges Axsome may face when seeking approval, considering both the successful and non-significant trial results?

AXS-05 targets the NMDA receptor and sigma-1 receptor pathways, both implicated in agitation and neuropsychiatric symptoms. Do the trial results align with the proposed mechanism of action, and how could this affect its broader applicability beyond Alzheimer's agitation?

The long-term safety trial included over 300 patients treated for 6 months and 100 for over a year. What insights do these findings provide for the chronic management of agitation, and could they influence treatment guidelines?

With the ACCORD-2 trial showing significant efficacy while ADVANCE-2 did not, what additional data would be most critical for the continued development of AXS-05? Could further subgroup analyses or biomarker studies help clarify its role in Alzheimer’s care?