FDA panel rejects MDMA therapy for PTSD due to unclear data and safety concerns

Medical experts advising the Food and Drug Administration (FDA) expressed skepticism about MDMA's readiness to treat post-traumatic stress disorder (PTSD) and urged the agency to delay its approval. This recommendation came during a meeting held to review a new drug application submitted by Lykos Therapeutics, a California-based biotech firm.

Lykos has been investigating MDMA, also known as ecstasy or midomafetamine, for several years. Their clinical trials indicated that MDMA could significantly benefit PTSD patients when combined with psychotherapy. However, apprehensions regarding the methodology of these trials and MDMA's safety led the advisory panel to vote 9-2 against its efficacy for PTSD and 10-1 against its safety, implying the risks might outweigh potential benefits.

"I’m not convinced at all that this drug is effective based on the data I saw," said Rajesh Narendran, chair of the committee and a psychiatry professor at the University of Pittsburgh. Although the FDA is not obliged to follow its advisory panels' recommendations, it usually does. A final decision on Lykos' application is expected by August 11.

If approved, MDMA would be the first psychedelic-assisted therapy available in the U.S. and the first new PTSD treatment sanctioned by the FDA in over two decades. This context heightened the panelists’ awareness of the precedent they might set for future psychedelic research. Maryann Amirshahi, a panelist and emergency medicine professor at Georgetown University, emphasized the need for caution.

Currently, PTSD treatment primarily involves SSRIs, which can take months to show effects and have a response rate below 60%. The unmet needs of PTSD patients, who number around 13 million annually in the U.S., were highlighted by Kelly O’Donnell from the NYU Langone Center for Psychedelic Medicine during Lykos' presentation. She stressed the dire consequences of inadequate treatment options.

Lykos' two pivotal trials involved nearly 200 individuals with moderate to severe PTSD. Participants underwent three treatment sessions over 18 weeks, and those receiving MDMA showed a roughly 10-point reduction in symptom severity compared to the control group. O’Donnell, who collaborated with the trial's therapists, noted the rapid and meaningful improvements in patients, such as better sleep and enhanced self-worth.

Despite testimonials from trial participants and advocates underscoring the necessity for new PTSD treatments, especially for veterans, the panel's vote suggests approval is uncertain. Both the FDA and its advisers criticized several aspects of Lykos' trial data collection and analysis. Concerns included the lack of participant diversity, the insufficient characterization of MDMA's addictive potential, and the overall robustness of Lykos' findings.

A significant issue was the difficulty in maintaining a double-blind study due to MDMA's unmistakable effects, which most participants identified before the trials concluded. This "functional unblinding" might have skewed results positively. Narendran emphasized the necessity of accounting for participants' expectations in the analysis, calling the data "meaningless" without such adjustments.

Another point of contention was the concurrent psychotherapy all participants received, making it unclear how much of the benefit was attributable to MDMA. The FDA and experts questioned how Lykos would standardize the psychotherapy protocol if the drug were approved. Additional safety concerns about MDMA's impact on heart and liver functions were also raised.

Moreover, ethical concerns have clouded Lykos' case. In one earlier study, a participant alleged sexual misconduct by the treating psychiatrist and her unlicensed therapist husband. The Institute for Clinical and Economic Review (ICER) also claimed some therapists encouraged patients to report favorable outcomes while downplaying harms. These ethical breaches were echoed by several other study participants and researchers during the public hearing.

FDA officials, including Tiffany Farchione from the psychiatry drugs division, acknowledged these allegations and confirmed ongoing investigations. Kim Witczak, the panel's consumer representative, expressed serious doubts about the data's integrity and the misconduct allegations, stating she could not support the drug's approval given the reported harms and ongoing investigations.

In summary, the advisory panel's vote and the subsequent concerns about Lykos' trial methods, ethical conduct, and MDMA's safety have cast doubt on the immediate approval of MDMA for PTSD treatment by the FDA.