In her 2023 book, I Feel Love, journalist Rachel Nuwer charts the history of how MDMA ‘emerged from the shadows to the forefront of a medical revolution’. Of course, MAPS and Lykos have played a leadership role in this (re-)emergence. But I’m doubtful that either organisation is feeling a lot of love right now.
It doesn’t need rehashing here, as the regular reader will be aware of various thorns in the company’s side, perhaps most notably the damning appraisals from both ICER (see ICER Panel Rejects MDMA-Assisted Therapy, Highlights Evidence Gaps and Study Flaws in 14-1 Vote) and one of FDA’s own advisory committees (see Analysis: FDA Advisory Committee Snubs MDMA-Assisted Therapy for PTSD in Overwhelming “No” Vote).
The most pertinent question now, then, might be whether one side of the deliberative scales (two positive phase 3 studies, decades of MDMA use in the community and a relatively well characterised safety profile, the level of unmet need among PTSD patients and public awareness of this tragic fact, the agency’s interest in encouraging drug development in mental health, and other assorted factors that might contribute to political will for approval) might outweigh the other (gaps in Lykos’ NDA, publicised instances of misconduct and complaints of more, questions around the validity of the company’s study design and conduct and that of psychedelic research more generally).
While an increasingly factionalised psychedelics field has made landing on either side of these scales seem like an obvious choice or moral imperative—to the extent that those that come down on the other side of the scales are labelled as having blood on their hands, or are otherwise guilty for innumerable future suffering—in the eyes of the FDA, it really isn’t that straightforward.
With public trust in the FDA wavering and scandals like the opioid crisis well within the present zeitgeist, it’s looking at the scales with great pressure.
For the FDA, on one of the scales’ plates is well-publicised pressure to approve MDMA from a politically delicate group, veterans, as well as prominent figures like Elon Musk and Dan Crenshaw; expectation and desperation from healthcare providers and patients; intention to encourage continued development of innovative neuropsychiatric treatments; and so on.
On the other plate sits a whole other world of potential hurt for the agency. Approving MDMA could open up the agency to allegations of caving to lobbying and political pressure, being wooed by what some portray to be shoddy science, and ignoring the expertise of its own advisory committee. Now, this is not so much of a worry if MDMA-assisted therapy is ultimately rolled out in a safe and effective manner. But FDA will be imagining the worst-case scenarios, with things like the opioid and Aduhelm scandals top of mind.
All this to say, I certainly wouldn’t relish a seat on that FDA review team.
But FDA, which is privy to far more information and data than your humble correspondent, has a much clearer image of the NDA and associated program and launch plans than we do. After all, the agency has the power to request pretty much anything from the sponsor, with regards to the studies represented in the NDA, as part of specific inspections or in the general course of its reviewing the dossier.
Given that all of this takes place in private, however, it’s hard to imagine just how closely the agency is reviewing the program, or even which elements are under inspection.
According to reporting by Olivia Goldhill in STAT, for example, FDA hadn’t reached out to certain participants or their representatives in the course of those inspections, at least at the time of her writing. Goldhill said that this “raises questions about how the agency is pursuing the accusations, and whether a decision on the treatment could be delayed.”
Indeed, there are many questions.