FDA issues a Complete Response Letter for midomafetamine capsules for PTSD

The FDA communicated that it had completed its review of the NDA and determined that it could not be approved based on data submitted to date.

The FDA has requested that Lykos conduct an additional Phase III trial to further study the safety and efficacy of midomafetamine. Lykos plans to request a meeting with the FDA to ask for reconsideration of the decision and to further discuss the agency's recommendations for a resubmission seeking regulatory approval for midomafetamine capsules.

The issues expressed in the CRL echo those raised during the FDA Advisory Committee meeting on June 4, 2024. The Company and other stakeholders have expressed concerns around the structure and conduct of the Advisory Committee meeting, including the limited number of subject matter experts on the panel and the nature of the discussion, which at times veered beyond the scientific content in the briefing documents. FDA itself has acknowledged potential problems with the Advisory Committee process and has opened a public docket seeking comments on how it can be improved.

Lykos has previously published its response to the substantive issues discussed at the Advisory Committee hearing. Among others, this included concerns that Lykos' clinical data were insufficient to demonstrate durability along with questions about expectancy bias stemming primarily from participants with prior MDMA use. Lykos believes that the data included in the NDA provide sufficient evidence of efficacy and durability in line with the relevant FDA guidance. FDA's draft guidance for industry on psychedelic drugs indicates that endpoint data should be collected at 12 weeks; Lykos' Phase III studies collected endpoint data at 18 weeks, with additional exploratory endpoints collected six months or more later. In addition, Lykos had aligned with the FDA in the Special Protocol Assessment ("SPA") in 2017 on a variety of bias minimization measures in the study design. Prior MDMA use among participants was not previously viewed as detrimental. As an example, nearly 30% of participants in Lykos' Phase II studies reported prior use, which was shared with FDA before establishing the inclusion and exclusion criteria in the Phase III trial design.

The Advisory Committee panelists also raised psychotherapy as a concern, with some recommending to further characterize the extent to which psychotherapy contributes to treatment benefit and if it is even necessary. Lykos acknowledges that midomafetamine-assisted therapy represents a novel combination of drug and therapy that raises unique research questions and will continue to engage the FDA as appropriate on these challenges. Lykos remains committed to continuing development of this integrated approach.

"The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in over two decades," said Amy Emerson, Chief Executive Officer of Lykos Therapeutics. "While conducting another Phase III study would take several years, we still maintain that many of the requests that had been previously discussed with the FDA and raised at the Advisory Committee meeting can be addressed with existing data, post-approval requirements or through reference to the scientific literature."

Lykos will work diligently in the coming months to address FDA's concerns and to take advantage of agency processes to resolve scientific disagreements. Following the FDA meeting, Lykos expects to provide an update on next steps for the resubmission.