MindMed has announced that the FDA has granted Breakthrough Therapy designation to its MM120 program for generalized anxiety disorder (GAD). This decision follows positive results from a Phase 2b study, which demonstrated significant and durable reductions in anxiety symptoms after a single dose of MM120.
Phase 2b Study Results
The Phase 2b study of MM120 in GAD met its key secondary endpoint, showing clinically and statistically significant durability of activity through Week 12. The optimal dose of 100 μg resulted in a 7.7-point improvement over placebo on the Hamilton Anxiety Rating Scale (HAM-A) at Week 12 (-21.9 MM120 vs. -14.2 placebo; p<0.003, Cohen’s d=0.81). This dose also yielded a 65% clinical response rate and a 48% clinical remission rate sustained to Week 12.
Clinical Global Impressions - Severity (CGI-S) scores improved from 4.8 to 2.2 in the 100-μg dose group, indicating a shift from ‘markedly ill’ to ‘borderline ill’ at Week 12 (p<0.004). Improvements were observed as early as day 2, with further gains between Weeks 4 and 12.
Clinical Significance
"That MM120 exhibited rapid and robust efficacy, solidly sustained for 12 weeks after a single dose, is truly remarkable," stated Dr. David Feifel, Professor Emeritus of Psychiatry at the University of California, San Diego, and an investigator in the MM120 study. "These results suggest the potential MM120 has in the treatment of anxiety."
Breakthrough Therapy Designation
The FDA's Breakthrough Therapy designation is reserved for drugs that demonstrate preliminary clinical evidence of substantial improvement over available therapies for serious conditions. This designation will allow MindMed to engage more closely with the FDA to expedite the development and review process for MM120.
Next Steps
MindMed plans to hold an End-of-Phase 2 meeting with the FDA in the first half of 2024 and initiate its Phase 3 clinical program in the second half of 2024. These steps are crucial for further evaluating the safety and efficacy of MM120 and potentially bringing it to market.
About Generalized Anxiety Disorder
Generalized anxiety disorder (GAD) affects approximately 10% of U.S. adults, or around 20 million people. It is characterized by excessive, persistent, and unrealistic worry about everyday things. Despite the significant personal and societal burden of GAD, there has been limited innovation in treatment options in recent decades.
Study Design
The Phase 2b study, known as MMED008, was a multi-center, randomized, double-blind, placebo-controlled, dose-optimization trial. It enrolled 198 participants who were randomized to receive a single administration of MM120 at doses of 25, 50, 100, or 200 μg, or placebo. Participants had severe GAD symptoms, with average baseline HAM-A scores of approximately 30. Prior to treatment, participants were tapered off any anxiolytic or antidepressant treatments and did not receive psychotherapy during the study.
Safety and Tolerability
MM120 was generally well-tolerated, with most adverse events rated as mild to moderate, transient, and occurring on the dosing day. Common adverse events included illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis, and hyperhidrosis.
Mechanism of Action
Lysergide, the active ingredient in MM120, is a synthetic ergotamine that acts as a partial agonist at human serotonin-2A (5-HT2A) receptors. MindMed is exploring its potential applications in other serious brain health disorders beyond GAD.
