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Shroom Shmooz

FDA panel’s overwhelming hesitation on MDMA-AT. On June 4, at the end of a day of presentations (by Lykos and the FDA), public comments (the majority of which were supportive of the therapy), and discussion, the FDA’s Advisory Committee, comprising 11 experts, was required to vote on two questions. Do the available data show that the drug is effective in patients with PTSD? Do the benefits of midomafetamine (MDMA) with the FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD? For each question, the panel of advisors voted decisively in the negative by votes of 9-2 and 10-1, respectively. Panel voices its key concerns. The panel’s misgivings mimicked concerns raised by the ICER report, namely functional unblinding bias and an underreporting of adverse events, potentially biasing the recording of benefits and harms. Other concerns raised included the potential for abuse by therapists (based on one well-documented case that occurred in the Phase II studies) and the efficacy of the psychology behind the follow-up therapy sessions, which adds the complicating factor that psychotherapy does not come under the purview of the FDA approval process. But it leaves the door open. Amid the current overwhelming doubts reflected in the clearcut votes, this does not represent a complete rejection of Lykos’ MDMA-AT candidate for PTSD, but a call for Lykos to undertake further research on a therapy that ‘holds clinical promise’ for a condition with an urgent unmet need. What happens next? The FDA Advisory Committee’s assessment is not binding on the FDA, so the regulator can choose to ignore it and grant approval on August 11 (PDUFA date). There is some precedent for this outcome, but the FDA typically follows the panel’s recommendations. Statistics for the 2010-2021 period show that while the FDA concurs with virtually all the cases recommended for approval by the committee, there is a one-in-three chance that the FDA will go against the committee's advice in the cases where the latter has recommended against approval. Of the drugs that were approved, the median time between a positive vote and approval was 74 days, while the median time between a negative vote and approval was 700 days. Given the clearcut votes in this case, the FDA could request Lykos to do more work and provide more comprehensive data. The latter has indicated that it will collaborate with the FDA to address outstanding questions that could involve acceptance of undertaking more research. While the odds of getting MDMA-AT approval this year have probably lengthened, a possible scenario is that the regulator will permit MDMA-AT under ‘Emergency Use Authorization’, which is a limited authorization, as it did with restricted treatments for COVID-19 and like the current limited authorization permitting MDMA-AT under Canada’s Special Access Program.