First Patient Dosed in Phase 3 Study of Psychedelic MM120 in Generalized Anxiety Disorder

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MindMed announced the first patient had been dosed in the first-ever phase 3 trial of lysergic acid-diethylamide (LSD) for generalized anxiety disorder (GAD). MindMed is currently the furthest along in clinical trials exploring LSD as a treatment in multiple psychiatric indications, including major depressive disorder.^1,2

Building off a successful phase 2b study, the 52-week phase 3 study will enroll 200 participants and have 2 parts. The first 12 weeks will consist of a randomized, double-blind, placebo-controlled, parallel group period. The following 40 weeks will be an extension period; participants will be eligible for open-label treatment with MM120 ODT based on symptom severity.¹ The primary endpoint will measure the change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) score at week 12 for MM120 Orally Disintegrating Tablet (ODT) 100 µg vs placebo.

MM120 incorporates Catalent’s Zydis ODT fast-dissolve technology, meaning a more rapid absorption, improved bioavailability, and reduced gastrointestinal side effects.¹ The agent is a synthetic ergotamine, which acts as a partial agonist at human serotonin-2A (5-HT_2A) receptors.¹The FDA has granted Breakthrough Therapy Designation for the MM120 program in GAD based on the unmet need of treatment for GAD.If approved, this would be the first treatment for GAD approved since 1987.

The phase 2b dose range finding study tested 4 doses of MM120: 25 mcg, 50 mcg, 100 mcg, and 200mcg against placebo.³ Researchers found that after a single dose, patients who took a higher dose rapidly got better, according to MindMed's chief medical officer, Daniel R. Karlin, MD, MA. Patients continued to see improvement after 4 weeks, as measured on the HAM-A scale, as soon as week 1. Karlin told Psychiatric Times in an interview at the 2024 American Psychiatric Association annual meeting that 100 mcg was found to be the best dosage to bring forward, and that patients stayed better through week 12 after a single dose.³ Karlin said in a press release that phase 2 of the study “demonstrated efficacy that far exceeds today’s standard of care and a favorable tolerability profile.”¹

This step forward in the MindMed study hints at a promising future for the use of psychedelics in psychopharmacology, although many psychedelic agents remain schedule I narcotics, including LSD and cannabis. For example, a review of psychedelics as therapeutic options for diagnoses like mood and anxiety disorders noted that psychedelics “generally have low physiological toxicity, safe psychological responses, low addictive/dependence potential, low chance of neurological deficits after use and no associated persisting adverse physiological or psychological effects during or after use.”⁴

In a previous conversation with Psychiatric Times, Karlin said that he believes it is important to dispel prior beliefs and learn how LSD can be used in the future.⁵ LSD’s sociocultural influence may bias clinicians, patients, payers, and the FDA, and there has been much written about the best way to move forward.⁵

Nevertheless, Karlin is optimistic. “Today marks a pivotal moment in our journey towards advancing a novel treatment option for the 20 million people in the US living with GAD,” he said in a press release.¹

Psychiatric Times spoke with Daniel R. Karlin, MD, MA, in an exclusive video. Visit psychiatrictimes.com to learn more.

References

1. MindMed announces first patient dosed in phase 3 voyage study of MM120 in generalized anxiety disorder (GAD). Business Wire. December 16, 2024. Accessed December 16, 2024. https://www.businesswire.com/news/home/20241216046321/en/Duerr HA.

2. With MDMA on hold, what’s next for psychedelics? Psychiatric Times. September 10, 2024. Accessed December 16, 2024. https://www.psychiatrictimes.com/view/with-mdma-on-hold-whats-next-for-psychedelics

3. Karlin DR. Gad: A neglected diagnosis with a new investigational treatment. Psychiatric Times. May 7, 2024. Accessed December 16, 2024. https://www.psychiatrictimes.com/view/gad-a-neglected-diagnosis-with-a-new-investigational-treatment4. Lowe H, Toyang N, Steele B, et al. Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders. Molecules. 2022;27(8):2520. Published April 14, 2022. Accessed December 16, 2024. https://www.psychiatrictimes.com/view/psychiatrys-risky-gamble-on-recreational-drugs-the-royal-road-to-the-unconscious-or-down-a-pharmacologic-garden-path

5. Karlin DR. A fresh look at LSD. Psychiatric Times. May 7, 2024. Accessed December 16, 2024. https://www.psychiatrictimes.com/view/a-fresh-look-at-lsd