FDA Committee Rejects Lykos' MDMA Treatment Despite Near Approval

The FDA held a significant review on the potential approval of MDMA-assisted therapy for post-traumatic stress disorder (PTSD), marking the first time a psychedelic treatment has been considered by the committee. Lykos Therapeutics, the company behind the MDMA therapy, faced a setback as the Psychopharmacologic Drugs Advisory Committee voted overwhelmingly against recommending the treatment for approval.

The committee's votes focused on two critical questions: the efficacy of MDMA therapy in PTSD patients and whether the treatment's benefits outweigh its risks, given a proposed risk evaluation and mitigation strategy (REMS). The committee voted 9-2 against the therapy's effectiveness and 10-1 against its benefit-risk balance. Despite the committee’s advisory role, the FDA generally follows its recommendations.

Lykos Therapeutics aimed to secure approval for an MDMA capsule combined with psychological intervention for PTSD, known as MDMA-assisted therapy. Amy Emerson, Lykos CEO, expressed disappointment over the committee's decision, highlighting the urgent need for effective PTSD treatments. Emerson pledged to collaborate with the FDA to address remaining concerns and explore a viable path forward for the therapy.

The FDA expressed apprehensions about conducting unbiased clinical trials for MDMA due to the drug's significant effects on mood, sensation, and cognition, which complicate blinding in studies. Following a nine-hour deliberation, committee members unanimously agreed that current data is insufficient to support MDMA's market entry, though they acknowledged its potential.

Paul Holtzheimer, M.D., deputy director for research at the National Center for PTSD, emphasized the need for new treatments but cautioned against premature adoption. He noted that introducing a treatment too soon might hinder its proper development and optimal use. Walter Dunn, M.D., Ph.D., who cast the lone supportive vote for the benefit-risk question, expressed tentative support, acknowledging the immediate need for new PTSD treatments but also cautioning about the therapy's risks. Dunn stated that the psychotherapy component, while promising, also complicates the FDA's evaluation.

Dunn suggested that Lykos is on the right track but needs to address certain safety concerns. He emphasized the urgent need for new PTSD treatments, particularly for veterans, and believed MDMA could be safe in the right clinical context if the REMS issues were resolved. Dunn's vote was influenced by his background as a former service member and his understanding of veterans' needs.

Other committee members encouraged Lykos to continue its research efforts. Kim Witczak, a consumer advocate, commended both the FDA and Lykos for their rigorous examination of the application. Witczak acknowledged the progress made but indicated that more work is needed.

Lykos remains committed to pursuing approval for MDMA. The FDA is expected to make its final decision on the application by August 11. The application was supported by multiple studies, including six phase 2 studies, two phase 3 trials, and a long-term follow-up study. Both phase 3 trials demonstrated significant improvement in PTSD symptoms compared to placebo and psychological intervention.

Even if the FDA approves the treatment, further challenges lie ahead. MDMA, commonly known as ecstasy, is classified as a Schedule 1 substance, alongside drugs like heroin and marijuana. For MDMA to be used therapeutically, it would need to be rescheduled.

In summary, while Lykos Therapeutics faces significant obstacles in getting MDMA therapy approved for PTSD, the company remains resolute. The FDA committee's cautious stance underscores the need for further research to ensure both efficacy and safety before MDMA can be introduced into clinical practice.