Lykos Therapeutics, Inc. – FDA CRL

Lykos Therapeutics received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA 215455) for midomafetamine capsules for posttraumatic stress disorder (PTSD). The FDA concluded the application lacks substantial evidence of effectiveness and fails to establish product safety. A key issue was the unreliability of safety data; FDA inspections identified unreported adverse events and a systemic failure to document 'positive' or 'favorable' drug experiences as adverse events, hindering assessment of abuse potential, acute effects, and impairment duration.

Additionally, the application did not demonstrate a durable treatment effect beyond 18 weeks, essential for a chronic condition like PTSD. The follow-up study, MPLONG, was deemed inadequate due to significant design flaws, including variable visit timing, potential self-selection bias, and participants' use of other therapeutic interventions. Concerns were also raised about the generalizability of results, as approximately 40% of enrolled participants had prior midomafetamine experience, significantly higher than in the general PTSD population, suggesting selection and expectation bias. The FDA recommended conducting a new clinical trial to thoroughly assess durability of effect and adequately characterize the safety of midomafetamine.