FDA Panel Votes Against MDMA-Assisted Therapy

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The US Food and Drug Administration Psychopharmacologic Drugs Advisory Committee voted against the approval of MDMA-assisted therapy for the treatment for posttraumatic stress disorder (PTSD) last night, Tuesday June 4.

Panel experts weighed the need for new PTSD treatments against the concerns with data submitted by Lykos Therapeutics. While MDMA seemed to have a positive effect on many participants in the 2 phase 3 clinical trials, MAPP1 and MAPP 2, several issues swayed the vote in the negative. Cited reasoning included faulty study design and ethical violations.

One of the most vociferous concerns was the studies’ functional unblinding. In an analysis by FDA scientists, it was claimed that “profound alterations in mood, sensation, suggestibility and cognition,” which participants endured when treated with MDMA, impact the golden standard double-blinding: “As a result, studies are nearly impossible to blind.”¹ This was one of the major concerns of the panel. With this lack of double-blinding, panelists feared participants would anticipate an effect with MDMA, which could then “artificially inflate” results.

"Without accounting for what the expectation was, and somehow incorporating that into some kind of statistical model, I think it’s just meaningless,” said Rajesh Narendran, committee chair and psychiatry professor at the University of Pittsburgh. “I just feel very convinced that I had to vote no.”

The FDA panel also found the Lykos safety data did not adequately convey how MDMA affected participants' hearts. An adverse event concern was the increase of blood pressure and heart rate. During studies MAPP1 and MAPP 2, 46% of participants treated with MDMA vs 17% of participants treated with placebo had an increase in systolic blood pressure ≥20 mm Hg during the third of 3 medication sessions, and 45% of participants treated with MDMA vs 32% of participants treated with placebo had an increase in diastolic blood pressure ≥10 mm Hg during the third of 3 medication sessions.¹

Other issues included lack of diversity among participants, who were nearly all White; lack of a clear pathway for reporting patient harm; lack of standardization in terms of psychotherapy; and allegations of sexual misconduct.

“I have real concerns with the validity of the data and the allegations of misconduct,” said panelist Kim Witczak, representing consumer concerns. “I cannot in good conscious support something where this many harms are being reported.”

This vote marked the first time FDA advisers had to consider a Schedule I psychedelic for therapeutic use. It is considered a major setback for psychedelic advocates hoping to use the treatment across several mental health disorders. The FDA is not required to follow the vote of this advisory committees; however, it usually does. The final decision on Lykos’ application will come on August 11, 2024.

Reference

1. FDA briefing document #215455. Psychopharmacologic Drugs Advisory Committee Meeting. June 4, 2024. https://www.fda.gov/media/178984/download