Rapid and Durable Response to a Single Dose of MM120 (Lysergide) in Generalized Anxiety Disorder: A Dose-Optimization Study

Background: This study evaluated the dose-response relationship of efficacy, safety, and tolerability for single-dose MM120 (lysergide D-tartrate) vs placebo in participants with generalized anxiety disorder (GAD).
Methods: This phase 2b (NCT05407064) multicenter, randomized, double-blind, placebo-controlled study enrolled adults (18 to 74 years) diagnosed with GAD and moderate-to-severe anxiety as defined by a Hamilton Anxiety Scale (HAM-A) of ≥20). Participants were randomized equally to receive single dose MM120 at 25µg, 50µg, 100µg, or 200µg, or placebo. The primary objective assessed change in HAM-A from baseline to week (w) 4. Secondary endpoints included improvements in other efficacy measures, quality of life, and safety and tolerability.
Results: 198 participants were enrolled. MM120 100µg and 200µg doses demonstrated clinically and statistically significant efficacy. The 100µg dose achieved the highest level of clinical activity: 7.6 points in HAM-A compared to placebo at w4 (-21.34 MM-120 vs -13.75 placebo; P=0.0004). At w4, 77.5% of participants treated with MM120 100µg showed a clinical response: ≥50% improvement in HAM-A versus 30.8% with placebo. Clinical Global Impressions-Severity (CGI-S) scores improved by 1.8 points with MM120 100µg vs 0.7 points with placebo (P=0.0001) on day 2, which persisted through w4 (P < 0.01). Treatment-emergent adverse events occurred in 97.5% of participants in the MM120 100µg group vs 56.4% in placebo. Most events were mild to moderate, occurred on the dosing day, and were consistent with the expected effects of MM120.
Conclusion: These findings suggest a rapid and durable clinical response to MM120 with no identified safety concerns among participants with moderate-to-severe GAD.