FDA Panel Rejects Lykos’ MDMA-Assisted PTSD Therapy

The FDA’s Psychopharmacologic Drugs Advisory Committee has voted decisively against Lykos Therapeutics' proposed MDMA-assisted therapy for post-traumatic stress disorder (PTSD). The committee cited significant concerns with the biotech company's Phase III clinical trials for the investigational treatment.

In a 10-1 vote, the panel concluded that the potential benefits of Lykos' therapeutic candidate did not outweigh its risks, despite the implementation of a stringent risk evaluation and mitigation strategy. Additionally, the advisors voted 9-2 on the adequacy of the evidence provided, indicating that Lykos had failed to demonstrate sufficient efficacy data for its MDMA-assisted therapy in treating PTSD.

Kim Witczak, a consumer representative on the panel, expressed skepticism during the meeting. She highlighted issues such as selection bias and functional unblinding, suggesting that there were elements of potential misconduct and manipulation of trial results. This contributed to her vote against the therapy.

Elizabeth Joniak-Grant, who serves as a patient representative and quality research consultant at the Injury Prevention Research Center of the University of North Carolina, Chapel Hill, also found the decision challenging. While she acknowledged some of the data appeared promising, she raised concerns about the trial’s recruitment process. Notably, she pointed out that 40% of participants had prior experience with MDMA, which might have influenced the efficacy outcomes.

Despite the committee's recommendation, the FDA will continue to review Lykos' investigational treatment, with a target action date set for August 11, 2024. Although the FDA is not obligated to adhere to the advisory committee's advice, it generally does so.

Lykos is seeking regulatory approval to use MDMA—known scientifically as 3,4-methylenedioxymethamphetamine and commonly referred to as ecstasy—in oral tablet form for PTSD treatment, in combination with supportive mental health services such as psychotherapy.

The company's application is supported by two pivotal Phase III studies, dubbed MAPP1 and MAPP2. According to Lykos’ briefing documents, these trials indicated that the MDMA-assisted regimen led to "clinically meaningful improvements in PTSD symptoms," as measured by the Clinician-Administered PTSD Scale for DSM-5.

However, a recent report from the Institute for Clinical and Economic Review (ICER) has drawn attention to flaws in the design of Lykos' studies. The report highlighted concerns about the recruitment of patients with strong pre-existing beliefs regarding MDMA use, which could have biased the reporting of both benefits and harms. ICER also noted that there were pressures to report favorable results for Lykos' candidate.

In its briefing document for the advisory committee meeting, the FDA outlined significant shortcomings in the study designs. The trials, while intended to be double-blinded, suffered from "functional unblinding" due to the noticeable effects of the drug, which undermined the integrity of the blinding process.

The ongoing review by the FDA will ultimately determine the fate of Lykos’ MDMA-assisted therapy for PTSD. The outcome will have implications for both the future of MDMA as a therapeutic agent and the broader field of psychopharmacology.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!