FDA Advisory Committee Will Soon Meet to Discuss MDMA-Assisted Therapy for PTSD

The FDA’s Psychopharmacologic Drugs Advisory Committee will meet on June 4 to review a new drug application (NDA) from Lykos Therapeutics for midomafetamine (MDMA)-assisted therapy to treat post-traumatic stress disorder (PTSD).¹

FDA Advisory Committee Will Soon Meet to Discuss MDMA-Assisted Therapy for PTSD / Tada Images - stock.adobe.com

What’s the Issue?

The committee meeting will be the first to review a psychedelic-assisted therapy in the United States, as well as the first in 25 years to review a potential new PTSD treatment.

• The NDA from Lykos was accepted and granted priority review by the FDA on February 9, 2024. It was assigned a Prescription Drug User Fee Act (PDUFA) date of August 11, 2024.
• If approved by the FDA, it would be the first MDMA-assisted therapy and first psychedelic-assisted therapy in the country.
• MDMA (3,4-Methylenedioxy-methamphetamine), more commonly known as ecstasy, is an entactogen—a type of psychoactive compound that’s characterized by its ability to increase self-awareness. It is classified by the Drug Enforcement Agency as a Schedule I drug under the Controlled Substances Act.

READ MORE: The Psychedelic Pharmacy: A Paradigm Shift in Mental Health Treatment

Why it Matters

Since the Controlled Substances Act was passed in 1970 and federal drug schedules were made, most psychedelic substances were placed into Schedule I and were deemed to have no medical benefit. Not only would MDMA’s approval represent a historic shift in psychedelic medicine, but it could also “open the door to a potentially powerful new pathway to healing” for patients with PTSD, according to Bessel van der Kolk, MD.²

• PTSD, which develops after exposure to a potentially traumatic event, impacted 3.6% of adults in the US last year. The condition has a lifetime prevalence of 6.8%.³
• Patients with PTSD can experience persistent, frightening thoughts and memories, sleep problems, feel detached or numb, or may be easily startled. Severe forms can impair the ability to function at work, home, and socially.³
• Research has shown that over 30% of patients in the general population with PTSD are resistant to treatment, highlighting the critical need for new forms of therapy.⁴

Expert Commentary

• "This will be the first MDMA-assisted therapy and psychedelic-assisted therapy to be reviewed by the Psychopharmacologic Drugs Advisory Committee, a significant milestone in the field of psychedelic medicine, resulting from decades of clinical research and advocacy," Amy Emerson, CEO of Lykos Therapeutics, said in a release.¹ "We look forward to the opportunity to discuss the comprehensive data package of investigational MDMA and how, if approved, it may be used as a prescription treatment in combination with psychological intervention in adults with PTSD."
• “MDMA is an experiential therapeutic and therefore necessitates the appropriate set and setting to truly guide change and recovery,” Jennifer Mitchell, PhD, said in a release.² “While many forms of PTSD therapy involve recalling previous trauma, the unique ability of MDMA to raise compassion and understanding while tamping down fear is likely what enables it to be so effective.”
• “Thirty-eight years ago, one of my primary motivations for founding MAPS was to carve a path for psychedelic-assisted therapies to become FDA-approved treatments,” Rick Doblin, founder and president of the Multidisciplinary Association for Psychedelic Studies (MAPS), said in a release.⁵ “We hope that potential FDA approval of MDMA-assisted therapy for PTSD is only the first of many psychedelic-assisted therapies that become available by prescription.”

In Depth Insights

The FDA’s acceptance of Lykos’ NDA was based on data from 2 phase 3 clinical trials: MAPP1 (NCT03537014) and MAPP2 (NCT04077437).

• The randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of MDMA used in combination with psychological intervention versus placebo in patients diagnosed with severe or moderate to severe PTSD.
• MAPP1 included 90 participants randomly assigned to receive manualized therapy with MDMA or placebo, combined with 3 preparatory and 9 integrative therapy sessions. The study found that MDMA induced significant and robust attenuation in PTSD symptoms.⁶
• MAPP2 included 104 participants who were randomly assigned to MDMA-assisted therapy or placebo with therapy. The study found that mean changes in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score was -23.7 for MDMA, compared to -14.8 for placebo.⁷

Extra Reading

For more on this issue, check out these articles:

• Agony over ecstasy: FDA bid shows it’s hard to test psychedelics (Washington Post)
• MDMA-based mental health treatment faces wary US regulator (Financial Times)

READ MORE: Therapeutic Relationship Plays Key Role in Psychedelic Treatment

Reference

1. Lykos Therapeutics Announces FDA Advisory Committee Meeting to Review Investigational MDMA-Assisted Therapy for PTSD. News Release. Lykos Therapeutics. May 6, 2024. Accessed May 7, 2024. https://news.lykospbc.com/2024-05-06-Lykos-Therapeutics-Announces-FDA-Advisory-Committee-Meeting-to-Review-Investigational-MDMA-Assisted-Therapy-for-PTSD

2. MAPS’ Phase 3 Trial of MDMA-Assisted Therapy for PTSD Achieves Highly Statistically Significant Results for Patients with Severe, Chronic PTSD. News Release. Lykos Therapeutics. May 3, 2021. Accessed May 7, 2024. https://news.lykospbc.com/2021-05-03-MAPS-Phase-3-Trial-of-MDMA-Assisted-Therapy-for-PTSD-Achieves-Highly-Statistically-Significant-Results-for-Patients-with-Severe,-Chronic-PTSD

3. Post-Traumatic Stress Disorder (PTSD). Report. National Institute of Mental Health. Accessed May 7, 2024. https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd

4. Committee on the Assessment of Ongoing Efforts in the Treatment of Posttraumatic Stress Disorder; Board on the Health of Select Populations; Institute of Medicine. Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Final Assessment. Washington (DC): National Academies Press (US); June 17, 2014.

5. MAPS Congratulates Lykos Therapeutics on Acceptance of New Drug Application for MDMA-Assisted Therapy for PTSD. News Release. MAPS. February 9, 2024. Accessed February 12, 2024. https://maps.org/2024/02/09/maps-congratulates-lykos-on-acceptance-of-new-drug-application/

6. Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033 (2021). https://doi.org/10.1038/s41591-021-01336-3

7. Mitchell, J.M., Ot’alora G., M., van der Kolk, B. et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med 29, 2473–2480 (2023). https://doi.org/10.1038/s41591-023-02565-4