'It just needs to be better studied': FDA advisory committee rejects MDMA for PTSD

Key takeaways:

• The Psychopharmacologic Drugs Advisory Committee rejected MDMA-assisted therapy as a PTSD treatment.
• Members said MDMA is promising but there was insufficient evidence to support a recommendation for approval.

An FDA advisory committee voted against recommending a psychedelic treatment for PTSD, citing insufficient data for what many described as a still-promising path forward.

The Psychopharmacologic Drugs Advisory Committee met June 4 to discuss a new drug application for midomafetamine (MDMA) — submitted by Lykos Therapeutics, formerly MAPS Public Benefit Corporation. It was the first FDA advisory committee meeting to evaluate a new PTSD treatment in 25 years, and the first time that committee members considered a psychedelic treatment for PTSD.

Despite the widespread prevalence of PTSD, there are “very few medications approved for this indication,” which has driven interest in new treatment possibilities among both patients and providers, David Millis, MD, a clinical reviewer for the agency, said.

“Off-label treatment for PTSD is common, with a number and range of off-label treatment options, possibly a reflection of the limitations of the approved treatments,” Mills said. “The applicant is proposing a novel treatment paradigm.”

In mid-February, the FDA granted priority review to the new drug application, which states that the drug would be used in combination with a psychological intervention.

The application generated some controversy, which was reflected in the public comment portion of the meeting. While some endorsed the application — a few veterans described firsthand experiences of the drug’s benefits, even crediting it as a life-saving medication — others heavily criticized Lykos, arguing that the research is spiritually based and citing inappropriate behavior in clinical trials that is currently under investigation.

In the following discussion, several committee members also expressed concerns about the alleged misconduct, as well as gaps in data, the diversity of the study population, functional unblinding in the trials and inconsistencies in the proposed psychological intervention.

Elizabeth Joniak-Grant, PhD, a sociologist and qualitative research consultant with the University of North Carolina, Chapel Hill’s Injury Prevention Research Center, said that, while she is “somewhat convinced of MDMA’s effectiveness,” she had concerns regarding the specific evidence presented to the committee.

“I think this is a promising pathway; I think most of us probably think that,” Joniak-Grant, temporary voting member of the committee, said. “But also, I can’t in good conscience support something where this many harms are being reported and just say, ‘Oh, someone somewhere is investigating it and I’m sure it will be taken care of.’”

When asked whether the available data show MDMA-assisted psychotherapy is effective in patients with PTSD, nine committee members voted “no” and two members voted “yes.”

When asked whether the benefits of MDMA-assisted psychotherapy outweigh its risks, 10 members voted “no” and one voted “yes.”

The FDA is expected to make its final decision in August.

“Similar to many of my colleagues, I felt that the large positive effect was denoted by the significant confounders,” Maryann Amirshahi, PharmD, MD, MPH, PhD, a professor of emergency medicine at Georgetown University School of Medicine and co-medical director of the National Capital Poison Center, said. “Although I do believe there was a signal, it just needs to be better studied.”

References:

• June 4, 2024, Meeting of the Psychopharmacologic Drugs Advisory Committee. https://www.youtube.com/live/JqQKP8gcY1E. Accessed June 4, 2024.
• Lykos therapeutics announces FDA advisory committee meeting to review investigational MDMA-assisted therapy for PTSD. https://news.lykospbc.com/2024-05-06-Lykos-Therapeutics-Announces-FDA-Advisory-Committee-Meeting-to-Review-Investigational-MDMA-Assisted-Therapy-for-PTSD. Published May 6, 2024. Accessed June 4, 2024.