FDA Advisory Panel Votes Against MDMA-Assisted Therapy for PTSD

An independent FDA advisory panel voted against the use of midomafetamine (MDMA)-assisted therapy to treat post-traumatic stress disorder (PTSD) during a meeting held Tuesday, saying the treatment was not effective at treating the condition and that the benefits don’t outweigh risks associated with the drug.

FDA Advisory Panel Votes Against MDMA-Assisted Therapy for PTSD / monticellllo - stock.adobe.com

What’s the Issue?

The Psychopharmacologic Drugs Advisory Committee met to discuss the new drug application (NDA) from Lykos Therapeutics, which was accepted and granted priority review by the FDA on February 9, 2024.

• The advisory panel voted 9-2 that MDMA-assisted therapy to treat PTSD is not effective and 10-1 that the benefits of the treatment do not outweigh its risks.
• Much of the meeting’s discussion centered around 2 phase 3 clinical trials conducted by Lykos: MAPP1 (NCT03537014) and MAPP2 (NCT04077437). Both studies were randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of MDMA in combination with psychological intervention in patients diagnosed with severe or moderate to severe PTSD.
• Members of the panel raised concerns about the occurrence of functional unblinding in the studies, as well as adverse events that occurred, particularly around cardiovascular effects from the drug. Committee members also cited the lack of data on the potential for abuse as a major issue.

Why it Matters

The advisory panel meeting was the first to review a psychedelic-assisted therapy in the United States. Although the FDA does not have to follow the committee’s vote, the federal agency does usually base its decision on it.

• The panel’s vote against MDMA to treat PTSD represents a significant setback for proponents of psychedelic medicine, putting the potential approval of the first psychedelic in jeopardy, according to NPR.¹
• If approved, the NDA from Lykos—which was assigned a Prescription Drug User Fee Act (PDUFA) date of August 11, 2024—would be the first MDMA-assisted therapy and first psychedelic-assisted therapy in the country.
• PTSD, which impacts 3.6% of adults in the US, has not had a new treatment approved in over 25 years. Over 30% of patients in the general population with PTSD are resistant to currently available treatments.²

Expert Commentary

• “I absolutely agree that we need new and better treatments for PTSD,” said Paul Holtzheimer, a member of the panel, the New York Times reported.³ “However, I also note that premature introduction of a treatment can actually stifle development, stifle implementation and lead to premature adoption of treatments that are either not completely known to be safe, not fully effective or not being used at their optimal efficacy.”
• “I have real concerns with the validity of the data and the allegations of misconduct,” said Elizabeth Joniak-Grant, a member of the panel, NPR reported.¹ “I can't in good conscience support something where these many harms are being reported.”
• “There’s a recognition that psychedelics are probably uniquely susceptible to the blurring of the boundaries between strictly applied medical treatments that are provided by experienced clinicians under very well-monitored circumstances versus recreational use, so there’s a great interest in trying to get this as right as possible,” said Jon Alpert, chair of the American Psychiatric Association’s research council, CNN reported.⁴ “The last thing you want is for a promising treatment for a devastating condition to go off the rails in an unbounded, unmonitored kind of use.”
• "We are disappointed in today's vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention," Amy Emerson, CEO of Lykos, said in a release.⁵ "We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved.”

In Depth Insights

Since the Controlled Substances Act of 1970 and the creation of federal drug schedules, most psychedelic substances were placed into Schedule I and were deemed to have no medical benefit. Lykos’ approval would therefore represent a historic shift in psychedelic medicine.

• 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.

Extra Reading

For more on this issue, check out these articles:

• MDMA therapy for PTSD rejected by FDA panel (Nature)
• MDMA’s federal approval drama, briefly explained (VOX)
• Panel rejects psychedelic drug MDMA as a PTSD treatment in possible setback for advocates (AP)

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References

1. Stone W. FDA advisors reject MDMA therapy for PTSD, amid concerns over research. News Report. NPR. June 4, 2024. Accessed June 5, 2024. https://www.npr.org/sections/shots-health-news/2024/06/04/nx-s1-4991112/mdma-therapy-ptsd-fda-advisors

2. 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.

3. Jacobs A. F.D.A. Panel Rejects MDMA-Aided Therapy for PTSD. News Report. New York Times. June 4, 2024. Accessed June 5, 2024. https://www.nytimes.com/2024/06/04/health/fda-mdma-therapy-ptsd.html

4. McPhillips D. FDA advisers vote against first MDMA therapy to treat PTSD. News Report. CNN. June 4, 2024. Accessed June 5, 2024. https://www.cnn.com/2024/06/04/health/mdma-ptsd-fda-advisers/index.html

5. Lykos Therapeutics Provides Update on FDA Advisory Committee Meeting for Investigational MDMA-Assisted Therapy for PTSD. News Release. Lykos Therapeutics. June 4, 2024. Accessed June5 , 2024. https://news.lykospbc.com/2024-06-04-Lykos-Therapeutics-Provides-Update-on-FDA-Advisory-Committee-Meeting-for-Investigational-MDMA-Assisted-Therapy-for-PTSD