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A phase 2b clinical trial met its primary endpoint with positive topline results, showing MM-120 (lysergide d-tartrate) can reduce symptoms of generalized anxiety disorder, reflected in the Hamilton Anxiety rating scale scores.
Mind Medicine (MindMed) Inc. announced on Thursday, December 14th, a phase 2b clinical trial met its primary endpoint, finding MM-120 (lysergide D-tartrate or LSD) provided statistically significant and clinically meaningful improvements for generalized anxiety disorder (GAD).1
MM-120 is a synthetic tryptamine, a type of psychedelic, which serves as a partial agonist at human serotonin 2-A receptors. The drug is the tartrate salt form of lysergide. Last year, the US Food and Drug Administration cleared MindMed’s Investigational New Drug Application of MM-120 for generalized anxiety disorder, allowing the investigators to move forward and conduct a phase 2b dose-optimization trial.2
“It’s really sort of revolutionary,” Rishi Kakar, MD, chief scientific officer and associate medical director for Segal Trials, told HCPLive. “Here we are studying the dose response.”
In the phase 2b trial, a multi-center, parallel, randomized, double-blind, placebo-controlled, dose-optimization study, the investigators randomized 198 participants to receive a single administration of MM-120 at the doses of 25, 50, 100, 200 µg, or placebo.1 People could enroll if they had severe generalized anxiety disorder symptoms, with an average Hamilton Anxiety Rating Scale (HAMA-A) score of about 30. The primary endpoint was to see how the medication changed the HAM-A score from baseline to week 4. For the secondary endpoint, the investigators assessed after 12 weeks anxiety symptoms; the drug’s safety, tolerability, efficacy; and quality of life.
MM-120 100 µg significantly reduced HAM-A by 21.3 points, showing a 7.6 improvement from placebo to week 4 (P = .0004; Cohen’s d effect size = .88). The team observed a clinical response rate of 78% in the doses 100 µg and 200 µg, and a 50% clinical remission rate in the 100-dose group µg at week 4.
The Clinical Global Impressions – Severity (CGI-S) scores showed statistically significant and clinically meaningful improvements compared to placebo in the 100 µg (P ≤ .001) and 200 µg (P≤ .01) dose groups, with a 2-unit improvement.
Overall, MM-120 was well-tolerated with only mild-to-moderate adverse events and high completion rates. For the 4 weeks, 90% completed the study, and 97.5% reached the fourth week in the high-dose groups. Also, no participants in the high-dose groups discontinued due to adverse events. Some adverse events people faced on dosing day were illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paranesthesia, dizziness, tremors, nausea, vomiting, feeling abnormal, mydriasis, and hyperhidrosis.
In an interview with HCPLive, MindMed Chief Officer Daniel Karlin, MD, from University of Colorado School of Medicine, discussed the positive topline results of the phase 2b clinical trial—and why the data is important for clinicians to know about.
“For the last 30 years, really, since the development of Prozac and Zoloft and the commercialization of those drugs, there has been a lot of focus on depressive disorders like major depression, and less focus on generalized anxiety disorder, even though prior to that GAD—and other anxiety disorders—were considered mainstay of psychiatry,” Karlin said. “The focus on MDD has led there to be a lot less attention on GAD, and so there haven't been very many new treatments developed in that time for GAD.”
Karlin said cymbalta was the last drug approved for generalized anxiety disorder, back in 2004. Yet, as Karlin pointed out, there has been “renewed attention” on anxiety in the past 5 years, partly due to the pandemic.
“Even in the last year, the US Preventive Services Task Force or USPS DF recommended that all adolescents, children, and adults be screened for anxiety disorders,” Karlin said. “And so, we were increasingly recognizing that there are a lot of people walking around, feeling a ton of anxiety, who either aren’t getting treatment, often because they don't think anything will help them. Or if they are getting treatment, the treatment isn’t doing enough, that they’re still feeling badly despite being treated with the best available treatments.”
MM-120 stands apart from other generalized anxiety disorder medications because it is administered with a single dose. With just 1 dose, 50% of participants were in full remission from their disease in 4 weeks.
“This is a game changing paradigm for how people could be treated with GAD,” Karlin said. “The way that MM-120 is different from existing treatments is that currently, for drug-based treatments for pharmacotherapies, there’s no available treatment that represents something you could take once and then feel better for a substantial period of time afterward.”
With current treatments, individuals must take a drug daily and may see less of an effect size over time. By continuously taking medication daily, they also can have persistent adverse effects.
“Over time, for many people, the benefit that they get from the currently available treatments doesn’t make it worth it to have to go through the downsides of the currently available treatments,” Karlin said. “And again, that’s not true for everybody, and some people have great outcomes. And so, we don’t want to discourage anyone from getting the best treatment they can today, but our hope is that we’re able to add this drug to the available treatments so that people have a new option that works differently and that works durably and that works very quickly.”
Unlike other anxiety medications, MM-120 was not paired with psychotherapy. Karlin explained they left out psychotherapy so they could prove the drug works on its own.
“In our clinical studies, we will not do psychotherapy…but that doesn't mean that we think that in the real world, if and when we get a label for the drug and it’s approved, that people wouldn't be able to do psychotherapy before and after, even during a drug experience,” Karlin said. “We just thought was really important to develop the drug in this way, so that we could show that the drug itself works. So, if there’s one big difference in what we’ve done from what you might be seeing in the in the press or in the scientific literature about studies in this field, that’s probably the biggest difference in the way we ran this study.”