Robert Barrow, Chief Executive Officer of MindMed
The month of May is Mental Health Awareness Month, and an appropriate time to shine a spotlight on a mental health disorder that has been underserved and underacknowledged for too long.
On May 4, MindMed presented results from our Phase 2b clinical trial evaluating MM120, our proprietary, pharmaceutically optimized form of lysergide D-tartrate, in nearly 200 patients living with Generalized Anxiety Disorder (GAD). This presentation at the American Psychiatry Association (APA) annual meeting – the largest psychiatry-focused scientific meeting in the world – marks a significant milestone in our efforts to highlight the under-appreciated burden of disease that results from GAD.
The Burden of GAD
GAD afflicts millions of individuals, families, and communities at an alarming rate. GAD patients face substantial unmet need in alleviation and management of symptoms after almost two decades without progress toward new treatment options.
New epidemiological data also presented by MindMed at APA shows just how aggressively GAD has grown, with over 40% growth in US adults since the start of the pandemic. At MindMed, we believe that this growth strongly supports screening the general population for anxiety as recommended by the US Preventive Services Task Force (USPSTF), indicating that using the clinically validated GAD-7 screening tool would identify about three-fold more people living with anxiety than are currently diagnosed in the US.
Another MindMed study compared diagnosed and undiagnosed people with GAD to determine the condition’s relative impact on their lives. This study determined that the clinically meaningful impact of GAD was more significant among undiagnosed adults than their diagnosed counterparts. This difference was consistently noted across multiple factors: health-related quality of life, healthcare resource utilization, substantial activity impairment and work productivity loss.
Clinical Development of MM120 for GAD
Historically, the psychedelic drug class had shown great potential to offer robust, rapid, and durable efficacy, along with favorable safety and tolerability, for brain health disorders such as GAD. When a Sandoz researcher named Albert Hoffman first synthesized lysergic acid diethylamide (LSD or lysergide) in the 1930s, he created what would become the most studied and storied drug in the psychedelic class.
Today, MindMed is proud to build upon this extensive early body of research. We believe that our Phase 2b clinical trial of MM120 was the largest well-controlled study of lysergide and the most rigorous assessment of the dose-response relationship ever conducted. This study was a multi-center, parallel, randomized, double-blind, placebo-controlled, dose-optimization study that enrolled 198 participants randomized to receive a single administration of 25 µg, 50 µg, 100 µg or 200 µg of MM120, or placebo. Anxiety symptoms were measured for up to 12 weeks after MM120 administration using the Hamilton Anxiety Rating Scale (HAM-A), which is the gold standard in GAD. Uniquely, MM120 was administered as a single dose in a monitored clinical setting, with no additional therapeutic intervention. This approach allowed us to demonstrate MM120’s standalone drug effect instead of as simply a pharmacological catalyst for “psychedelic assisted therapy.”
Results from MindMed’s Phase 2b Study
In our study, MM120 demonstrated rapid, clinically meaningful, and statistically significant improvements on the HAM-A compared to placebo for up to 12 weeks after administration.
MM120 100µg – the dose with optimal clinical activity observed in the study – demonstrated a 7.7-point improvement over placebo at Week 12 (-21.9 MM120 vs. -14.2 placebo; p<0.003 Cohen’s d=0.81), with a 65% clinical response rate and a 48% clinical remission rate sustained to Week 12. Clinical Global Impressions - Severity (CGI-S) scores on average improved from 4.8 to 2.2 in the 100µg dose group, representing a two-category shift from ‘markedly ill’ to ‘borderline ill’ at Week 12 (p<0.004). This clinical activity was rapid, observed as early as study day 2, and durable with further improvements observed in mean HAM-A or CGI-S scores between Weeks 4 and 12.
One of the study’s secondary endpoints was the change from baseline compared to placebo in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, which measures the severity of depression symptoms. Major Depressive Disorder (MDD) and depressive symptoms are common co-morbidities in people with GAD. MADRS score improvements in the 100 µg arm of the study were clinically and statistically significant compared to the placebo group, with a difference of 5.7 points (p≤0.05) at week 4 and a difference of 6.4 points (p≤0.05) at week 12.
MM120 was generally well-tolerated, with most adverse events rated as mild to moderate, transient, and occurring on the dosing day (day 1) and being consistent with the expected acute effects of the study drug. The most common adverse events, with at least 10% incidence on dosing day in the 100µg dose group, included illusion, nausea, headache, hallucination, euphoric mood, anxiety, mydriasis, hyperhidrosis, paresthesia, fatigue, blood pressure increase, abnormal thinking, and altered state of consciousness.
Prior to treatment with MM120, study participants were clinically tapered and then washed out from any anxiolytic or antidepressant treatments and were not provided study-related psychotherapy for the duration of their participation in the study.
FDA Breakthrough Designation
Based on the significant unmet medical need in the treatment of GAD – especially in patients who do not respond to or tolerate currently available medications – along with the initial clinical data from our Phase 2b trial and other research conducted by MindMed, the U.S. Food & Drug Administration (FDA) has designated MM120 for GAD as a breakthrough therapy.
We believe that the FDA’s decision to designate MM120 as a breakthrough therapy for GAD and the durability data from our Phase 2b study provide further validation of the important potential role this treatment can play in addressing the huge unmet need among individuals living with GAD. At MindMed, we are committed to bringing MM120 to people living with GAD and delivering on the potential of our pipeline to treat serious brain health disorders.
The editorial staff had no role in this post's creation.