Opinion: Reflections on the Recent FDA Advisory Committee Review of MDMA-Assisted Therapy for PTSD
By Amil Patel
The recent meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) to review Lykos Therapeutics’ MDMA-assisted therapy for PTSD brought forth expected outcomes and highlighted several key concerns. As someone committed to enhancing equitable access to safe and supportive psychedelic therapies, I’d like to share my insights and reactions to the proceedings. The themes of concern raised during the meeting are crucial as they reflect both the challenges and opportunities inherent in this new frontier of healthcare.
Key Concerns Related to the Therapy Component
One of the primary concerns discussed was understanding the role of psychological support in the efficacy of MDMA-assisted therapy (MDMA-AT) and how this can be standardized. The FDA has consistently maintained that it lacks the authority to oversee psychological support, which isn’t surprising—they're oversight is specifically around the safety and efficacy of the medication. What Lykos is committed to pursuing is entirely new—using a medication as a tool to enhance psychological support—and the complexity of regulating such an integrated approach is evident.
The role of psychological support in the durability of MDMA-AT’s effects remains unclear. This is straightforward and unsurprising, and although the FDA has worked in collaboration with Lykos on the structure of the clinical trials, there remain valid questions on how to discern if the psychological support impacts treatment durability, as well as if the type of psychological support has a material impact. In this context, Lykos has maintained that the psychological support component is included specifically for patient safety, and it will be interesting to see how the FDA navigates oversight of this aspect. Untangling medication administration from psychological support seems unlikely, given the established context of safety.
Key Concerns Related to Safety
Safety concerns were another focal point, with the need for postmarketing studies to address issues such as cardiac safety, abuse potential, and data completeness. The absence of measured EKGs for cardiac safety and concerns around abuse potential were highlighted. Additionally, issues with data completeness, such as measuring baseline clinical lab data and omitting positive adverse events like euphoria, were noted. The long-term follow-up study (MPLONG) also faced attrition issues.
Both the FDA and Lykos have taken responsibility for gaps, and there seems to be a clear path to remediation. Implementing baseline labs as part of the Risk Evaluation and Mitigation Strategy (REMS) and continuing postmarketing studies are viable solutions to address these safety concerns.
Key Concerns Related to Effectiveness
The effectiveness of MDMA-AT was questioned due to issues with functional unblinding and its impact on study results. This challenge is likely to affect the broader field of dissociative psychedelics, not just Lykos. The committee took issue with some participants' prior experience with MDMA, which might have influenced their expectations and, consequently, the study results.
However, this concern is not unique to Lykos but is inherent in the effort to delineate the effects of dissociative psychedelic therapies from placebo.
A Promising Path Forward
Overall, the outcomes of the meeting were as anticipated, with no material surprises. The results could act as a catalyst for the FDA to develop a broader strategy for addressing these issues, which are specific not only to Lykos but also to the emerging class of psychedelic-assisted therapies. We applaud Lykos for pioneering this space and remaining steadfast in combining psychological support with medication.
It is also noteworthy that the FDA can still proceed with approval, independent of the advisory committee’s recommendations, as seen in previous cases like Aduhelm, eteplirsen, and selinexor. The path ahead remains promising, and today’s results reaffirm the importance of continued innovation and rigorous evaluation in the development of groundbreaking therapies.
This is just my initial reaction to the FDA Advisory Committee's all-day review of MDMA-assisted therapy for PTSD. We'll be digging deeper into the results and sharing more insights as we go.
One study participant, a military veteran from Colorado named Nick Brown, said, “I was fortunate enough to enroll and get accepted, ultimately changing my life forever.” He went on to describe how the treatment gave him self-compassion and allowed him to “get better sleep, have better relationships, and live what feels like a completely new life.”
This is worth getting right.
I wanted to extend a thank you to Josh Hardman and Psychedelic Alpha for their excellent live coverage of the committee review.