Casey Paleos, MD: Interpreting Trial Data and Safety for MDMA-Assisted Therapy in PTSD

As the calendar turns from July to August, the psychiatry community’s gaze now finds itself affixed to August 11 and the US Food and Drug Administration’s decision surrounding Lykos Therapeutics’ application for 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of posttraumatic stress disorder (PTSD).

Despite backing from a pair of phase 3 randomized, double-blind, placebo-controlled trials in MAPP1 and MAPP2, MDMA-assisted therapy has encountered numerous hurdles on the way to this potential decision, including the historic stigma attached to use of MDMA as a result of its Schedule 1 controlled substance and, more recently, a negative outcome from a meeting convened by the FDA’s Psychopharmacologic Drugs Advisory Committee in early June.

As part of our ongoing coverage leading up to this historic FDA decision, we contacted leading subject matters in the field. In this video series, our audience can hear the perspective of Casey Paleos, MD, an adult psychiatrist in a New York-based private practice and the Chief Medical Officer of InnerMost PBC. In the following video series, Paleos, who also served as a principal investigator and study therapist for Lykos-sponsored phase 3 clinical trials of MDMA-assisted therapy in PTSD, offers his perspective on a group of 5 questions related to the upcoming August 11, 2024, PDUFA data for MDMA-assisted therapy in PTSD. The questions for each segment are as follows:

• Can you give a brief overview of current options and unmet need in PTSD?
• Can you discuss your interpretation of the data supporting MDMA-assisted therapy in PTSD, including concerns about safety?
• How can clinicians and researchers address the stigma associated with using MDMA in a therapeutic context to ensure broader acceptance and understanding?
• Regardless of the FDA decision on this one application, what is your outlook on the potential of psychedelic therapies in PTSD looking forward?
• What are the most pertinent unanswered questions surrounding MDMA-assisted therapy for PTSD?

In the video segment featured above, Paleos tackles the second question. In his response, Paleos discusses his surprise at the PDAC panel's focus on concerns seemingly unrelated to what he considers strong efficacy data from the phase 3 trials. He highlights that these trials showed significant benefits, with 86% of participants experiencing significant symptom reduction and 71% no longer meeting PTSD criteria. Paleos also addresses concerns about addictiveness and toxicity, emphasizing the difference between MDMA's limited exposure and daily drug use. He explains that the therapeutic effect comes from the psychological process facilitated by MDMA, not from the drug itself. Paleos also touches on therapist misconduct, stressing that while risks exist, they are not unique to MDMA-assisted therapy and are managed by professional regulations.

Relevant disclosures of interest for Paleos include Lykos Therapeutics, Fluency, Mindbloom, Nautilus Sanctuary, Nautilus Psychiatric Services, InnerMost PBC, and Journey Clinical.

References:

1. Lykos Therapeutics. Lykos Therapeutics announces FDA Advisory Committee meeting to review investigational MDMA-Assisted therapy for PTSD. Lykos Therapeutics - News Release Archive. May 6, 2024. Accessed August 5, 2024. https://news.lykospbc.com/2024-05-06-Lykos-Therapeutics-Announces-FDA-Advisory-Committee-Meeting-to-Review-Investigational-MDMA-Assisted-Therapy-for-PTSD.
2. Kunzmann K. FDA Psychopharmacologic Advisory Committee votes against supporting effectiveness of MDMA FOR PTSD. HCP Live. June 4, 2024. Accessed August 05, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd.