Functional and Sexual Disability and Quality of Life After One Dose of MM120 (Lysergide) in Adults With Generalized Anxiety Disorder

Background: A dose-response evaluation of single-dose MM120 (lysergide D-tartrate) investigated functional disability (FD), sexual dysfunction (SD), and quality of life (QoL) secondary outcomes 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. FD, QoL, and SD were assessed by the Sheehan Disability Scale (SDS); EQ-5D-5L and Pittsburgh Sleep Quality Index (PSQI); and Arizona Sexual Experiences Questionnaire (ASEX), respectively.
Results: 198 participants were enrolled. MM120 doses >100µg demonstrated consistent improvements in FD at weeks (w) 1-12. Optimal primary efficacy dosing (100µg MM120) demonstrated placebo-adjusted improvements in EQ-5D-5L utility index of 0.111, 0.081, and 0.116 points and in EQ5 visual analog scale (VAS) of 4.02, 5.41, and 6.04 points at w4, w8 and w12, respectively. Mean PSQI scores improved at w4, w8, and w12 across all groups, including placebo. At w12, there was considerable decrease from baseline in the proportion of participants who reported SD: for males with MM120 100µg (29.2% at baseline vs 10% at w12) versus placebo (15.4% at baseline vs 12.5% at w12), and for females with MM120 100µg (75% at baseline vs 46.2% at w12) versus placebo (50% at baseline vs 33.3% at w12).
Conclusion: QoL measures demonstrated clinically significant and durable changes in response to single-dose treatment with MM120.