FDA Rejects Application for Psychedelic Drug

The U.S. Food and Drug Administration (FDA or Agency) rejected the new drug application (NDA) for a drug marketing approval submitted by Lykos Therapeutics Inc. (Lykos) for its psychedelic MDMA drug on Aug. 9, 2024. Lykos submitted the application to secure FDA approval for use of the drug to treat post-traumatic stress disorder (PTSD). No other such psychedelic drug product is on the market.

According to the Lykos press release following the decision, FDA said that it had completed its review of the NDA and determined that the drug could "not be approved based on data submitted to date." As such, the Agency requested that Lykos conduct an additional Phase 3 trial to further study the safety and efficacy of its product. The statement notes that Lykos plans to request a meeting with FDA to ask for reconsideration of the decision and further discuss the Agency's recommendations for a new submission in order to get regulatory approval, and the company stated, "Lykos will work diligently in the coming months to address FDA's concerns and to take advantage of agency processes to resolve scientific disagreements."

In some ways, FDA's decision is not surprising. An FDA advisory committee in June 2024 found that Lykos had not proved that the drug was effective because patients could tell if they were receiving the MDMA therapy instead of a placebo and may have fared better as a result. The advisers also cited limited information regarding adverse events and potential clinical trial misconduct. FDA's recent ruling follows many of the advisory committee's findings. For example, in March 2024, the Institute for Clinical and Economic Review (ICER) issued a draft report saying it had "substantial concerns about the validity of the [Lykos trial] results." Citing what would become consistent flaws in the design of the trial, ICER said, "because of the effects of MDMA, the trials were, essentially, unblinded with nearly all patients who received MDMA correctly identifying that they were in the MDMA arm of the trials. This would always raise concerns about bias, but these concerns are particularly heightened as we heard from multiple experts about the very strong prior beliefs of those involved in the trials (as investigators, therapists, and patients) about the benefits of [the product]."

Approximately 13 million Americans suffer from PTSD each year, with women and disadvantaged groups suffering disproportionately. Support for the Lykos MDMA product was particularly voiced by veterans. In addition, members of the U.S. House of Representatives and the U.S. Senate expressed support.

FDA's decision applies only to the specific Lykos MDMA drug product. Holland & Knight expects continued support for psychedelics from policymakers. Congress, federal agencies – such as FDA, the U.S. Department of Veterans Affairs and National Institutes of Health – and even state governments will remain actively engaged in discussions around relevant issues.

Holland & Knight will continue to monitor developments in the days ahead.