FDA advisory panel votes against MDMA therapy for PTSD

On June 4, 2024, the United States FDA Psychopharmacologic Drug Advisory Committee met to discuss and evaluate a new drug application submitted by Lykos Therapeutics for midomafetamine (MDMA) capsules to treat post-traumatic stress disorder (PTSD). However, at the meeting, the panel voted against approval of the capsules, with 10 to 1 voting that the drug’s benefits did not outweigh its risks and 9 to 2 voting that the treatment was ineffective. While the FDA is not bound to the committee's advice, it often makes regulatory decisions that align with committee votes.

According to NBC News, this committee meeting marks the first time a Schedule I psychedelic was considered for medical use.

MDMA, also called ecstasy, is a psychoactive entactogen that is thought to increase self-awareness and empathy. The National Institute on Drug Abuse states that the synthetic drug can also act as a stimulant and hallucinogen, causing distorted perceptions, energizing effects, and enhanced sensory experiences.

Despite the dangers of its recreational use, some studies have looked at the potential of MDMA in treating PTSD.

For example, a Nature Medicine study published in September 2023 looked at MDMA-assisted therapy for moderate to severe PTSD. Researchers compared the assisted therapy to placebo by analyzing changes in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score and Sheehan Disability Scale (SDS) functional impairment score. MDMA-assisted therapy reduced CAPS-5 scores by roughly 23.7 points, while the placebo therapy only reduced the score by 14.8 points. Additionally, SDS scores declined more significantly for MDMA-assisted treatment, with a 3.3-point decline compared to 2.1 points.

Additionally, a study published in Diseases in December 2023 reviewed the evidence of MDMA treatment for treatment-resistant PTSD, theorizing that MDMA reduces PTSD symptoms by increasing levels of some neurohormones and modulating activity in brain regions that are linked to fear and anxiety.

Despite evidence from these studies and other data submitted to the panel, the advisory board was not convinced of the treatment's benefits.

While some professionals, such as Walter Dunn, MD, PhD, assistant clinical professor in the department of psychiatry at the University of California Los Angeles, voted in favor of the treatment and emphasized the dire need for new PTSD treatments, others could not get over the potential risks.

According to NBC News, Melissa Decker Barone, an adjunct assistant professor in the Department of Psychiatry at the University of Maryland School of Medicine, said: “It sounds like MDMA has really impacted a number of people in positive ways, but it seems that there are so many problems with the data.”

Amy Emerson, Chief Executive Officer of Lykos Therapeutics, commented on the decision in a press release, saying, “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. 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. We are grateful to the advocates, clinical trial participants, and people living with PTSD who shared their testimony in the open public hearing and through written comments, and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD."

While the FDA’s final decision is not expected until August, the administration is expected to reject the new drug application. However, Lykos Therapeutics may provide additional data and research to support approval, which could be subject to review from an advisory panel.