A single oral administration of MM120 (lysergide d-tartrate), an investigational lysergic acid diethylamide (LSD)–based medicine being developed by Mind Medicine Inc (MindMed), provided rapid and durable improvement in generalized anxiety disorder (GAD) in a phase 2B study.
At 12 weeks, 65% of patients treated with MM120 100 µg had a clinical response, defined as at least a 50% reduction in total scores on the Hamilton Anxiety Rating scale (HAM-A), and 48% achieved remission, defined as HAM-A total score ≤ 7.
“Improvements in anxiety were seen as early as study day 2, so the response was not only robust but also rapid and sustained, at least through 12 weeks,” Reid Robison, MD, psychiatrist and adjunct faculty at University of Utah, Salt Lake City, Utah, and principal investigator with Numinus, noted in an interview with Medscape Medical News.
“What was also interesting was that MM120 also led to rapid improvement in comorbid depressive symptoms,” said Robison.
The findings were presented on May 4 at the American Psychiatric Association (APA) 2024 Annual Meeting.
As previously reported by Medscape Medical News, promising topline data from the phase 2B clinical trial led the US Food and Drug Administration (FDA) to grant breakthrough designation to MM120 for GAD.
Few New Treatment Options
GAD is among the most common psychiatric disorders, affecting an estimated 10% of US adults, or 20 million people. The disorder is often underdiagnosed, and there’s been very little innovation in the treatment of GAD in the past several decades.
The phase 2B, multicenter, double-blind, placebo-controlled, dose-optimization study of MM120 enrolled 198 adults with moderate to severe GAD (mean baseline HAM-A scores of approximately 30). They were randomly allocated to receive a single dose of 25 µg, 50 µg, 100 µg, or 200 µg of MM120 or placebo.
MM120 was administered as a single dose in a monitored clinical setting with no additional therapeutic intervention. Before starting treatment with MM120, study participants were clinically tapered and then washed out from any anxiolytic or antidepressant treatments and did not receive any form of study-related psychotherapy for the duration of their participation in the study.
A single dose of MM120 100 µg, the dose with optimal clinical activity observed in the study, demonstrated a 7.7-point improvement compared with placebo at week 12 (-21.9 with MM120 vs -14.2 with placebo; P < .003; Cohen’s d = 0.81), with a 65% response rate and a 48% remission rate sustained at 12 weeks, according to a company press release.
On average, Clinical Global Impressions – Severity (CGI-S) scores improved from 4.8 to 2.2 in the 100 µg–dose group. This represents a two-category shift from ” markedly ill ” to ” borderline ill ” at week 12 (P < .004), ” which to me, is pretty striking, ” Robison told Medscape Medical News.
Also speaking with Medscape Medical News at the APA meeting, Daniel R. Karlin, MD, MA, chief medical officer of MindMed, noted that in an anonymous survey conducted after the trial, some people described, “just being different after a single treatment, having a different relationship to their anxiety.”
Based on post-treatment patient responses, “it looks like a state change, something that shifts their relationship with anxiety — unlike an anxiolytic, a benzo, or a glass of wine — and it doesn’t look like a decaying improvement.”
MM120 also showed promising results on the key secondary endpoint of change from baseline compared with placebo on the Montgomery-Åsberg Depression Rating Scale (MADRS) scores, which measures the severity of depression symptoms.
MADRS score improvements in the 100-µg group were clinically and statistically significant compared with the placebo group, with a difference of 5.7 points (P ≤ .05) at week 4 and a difference of 6.4 points (P ≤ .05) at week 12.
Phase 3 Study in the Works
MM120 was generally well-tolerated. Most adverse events were rated as mild to moderate and transient and consistent, with the expected acute effects of the study drug.
The most common adverse events that occurred on dosing day were illusion (60%), nausea (40%), euphoric mood (27.5%), headache (25%), visual hallucination (22.5%), mydriasis (20%), altered state of consciousness (12.5%), anxiety (10%), blood pressure increase (10%), and abnormal thinking (10%).
Mild to moderate suicidal ideation developed in one participant in the 25-µg group and two in the 50-µg and 100-µg groups; however, none of these occurred on dosing day. One individual in the placebo group had moderate suicidal ideation on the dosing day.
“We will have an end of phase 2 meeting with the FDA this quarter and then launch the phase 3 program in the second half of the year,” Karlin told Medscape Medical News.
Commenting on the research for Medscape Medical News, Lisa M. Harding, MD, assistant clinical professor of psychiatry, Yale University School of Medicine, New Haven, Connecticut, said that GAD is a “prevalent comorbid psychiatric disorder” and that she “welcomes further studies looking at safety and tolerability” of MM120.
“The occurrence of illusion, euphoric mood and visual hallucination and suicidal ideation are of special concern among the treatment-emergent adverse events mentioned that remind us that the patients have to be appropriately screened and treatments have to be done in clinically supervised settings,” said Harding.
The study was funded by Mind Medicine, Inc. Karlin is an employee of the company. Robison is employed by Numinus and has stock ownership in Numinus. Harding has no relevant disclosures.