Axsome Therapeutics (AXSM) Study Result summary

Study Design and Scope

• Four pivotal Phase 3 trials (ADVANCE-1, ADVANCE-2, ACCORD-1, ACCORD-2) evaluated AXS-05 for agitation in Alzheimer's disease, using both parallel group and randomized withdrawal designs, with nearly 900 patients enrolled and long-term safety assessed in 456 patients up to 12 months.

• Trials included diverse patient populations aged 65–90 with probable Alzheimer's disease and clinically significant agitation.

• ACCORD-2 used a randomized withdrawal design with an open-label AXS-05 phase followed by randomization for sustained responders; ADVANCE-2 was a parallel-group trial with direct randomization to AXS-05 or placebo.

Efficacy Results

• ACCORD-2 met its primary endpoint, with AXS-05 significantly delaying time to relapse of agitation (hazard ratio 0.276, p=0.001) and reducing relapse rates (8.4% vs 28.6%, p=0.001).

• AXS-05 significantly prevented worsening of overall Alzheimer's severity compared to placebo (13.3% vs 39.3%, p<0.001).

• ADVANCE-2 did not reach statistical significance on the primary endpoint, though numerical improvements favored AXS-05 on primary and most secondary endpoints.

• Previous trials (ADVANCE-1, ACCORD-1) also met primary endpoints, supporting efficacy.

• In the open-label phase, 69% of patients achieved ≥30% reduction in agitation at 6 weeks, and 78% showed improvement on clinician-rated scales.

Safety and Tolerability

• AXS-05 was well tolerated in both short- and long-term studies, with adverse event rates similar to placebo and no deaths, cognitive decline, or new safety signals observed.

• Most common adverse events were headache, dizziness, and somnolence, with low rates of falls and serious adverse events.

• Discontinuations due to adverse events were low (<1%), and long-term safety data showed consistent tolerability.

• In long-term safety data (up to 12 months, n=456), headache was the only adverse event in ≥5% of subjects; serious adverse events were rare and unrelated to study drug.