Recent positive data from a phase III clinical trial of MDMA assisted psychotherapy for the treatment of post-traumatic stress disorder has fuelled excitement around Lykos Therapeutics’ bid to become the first company to obtain FDA marketing authorisation for a psychedelic drug.
However, in the latest development of this saga, an FDA advisory committee has dealt a significant blow to the hopes of commercialising MDMA. The panel of 11 independent experts voted 9-2 that the available data do not show that the drug is effective, and 10-1 that the benefits of MDMA do not outweigh the risks.
The advisory committee weighed a number of challenges. One of the most notable being the “functional unblinding” of the treatment arms owing to the profound effects of the drug. In one of the earlier studies, 90% of those in the treatment arm and 75% of those in the placebo arm correctly guessed their prescribed intervention. Members of the panel argued that this could have led to biases that skewed the results of the trial. The panel was also concerned about risks to the patients. The fact that one of the patients in an earlier trial was sexually abused by their therapist brought safeguarding of vulnerable patients into focus and it was also debated to what extent MDMA use could lead to an addiction risk.
However, the decision of the advisory committee has drawn sharp criticisms from those at the forefront of the psychedelics field, in particular the lack of experts on the panel with experience in psychedelics was one snag that drew attention. Apparently, at times during the meeting, committee members seemed unsure about whether and how to evaluate the psychotherapy part of the treatment. Voices of those working in the field of psychedelics say it does not make sense to assess the impact of the intervention without taking into consideration the talking therapy.
It may also be that lack of familiarity made the expert panel uncomfortable. For example, psychotherapy is not regulated by the FDA, indeed there is no general federal or state level regulation of talking therapies. Consequently, there were concerns that the application of talking therapies could lack consistency between clinical settings. Additionally, the lack of a clear biological mechanism to explain the results of treatment could have made it more difficult for the committee to believe the results of the clinical trials.
While the negative decision of the advisory committee is a serious knock to Lykos’ commercial plans, the vote is not binding on the FDA. Many of the key players hold out hope that the FDA will not follow the committee’s advice, but the odds are against them. Historically, the FDA has followed a negative decision of an advisory committee on an initial approval about 2/3 of the time. Nevertheless, Amy Emerson, CEO of Lykos remains steadfast, saying “[w]e really believe in the FDA's ability to assess the information and go through their process.”
Throwing fuel on the fire, a report from the Institute for Clinical and Economic Review that suggested that therapists may have encouraged favourable reports by patients and discouraged negative reports cast a dark shadow over the meeting. Unsurprisingly, the FDA is concerned by these allegations and is conducting an investigation which is to be completed before the FDA’s decision date of 11 August 2024.
In the meantime, the cloud of uncertainty that now surrounds psychedelics appears to have spooked investors; possibly contributing to a downward trend in the share prices of many publicly traded psychedelics firms such as MindMed, Atai Life Sciences, Cybin, Compass Pathways, GH Research, and Seelos Therapeutics.
Whatever the actual direction of the FDA decision, it’s set to be highly influential. Issues around blinding and psychotherapy have the potential to affect nearly every psychedelic currently in development. Approval could highlight a pathway for many other new and innovative treatments. On the other hand, a refusal could come with useful guidance on how the underlying clinical research could or should be conducted to ensure that the resulting data is convincing. The rationale of the FDA in this case could set major precedents for the future.
