FDA Rejects Application for MDMA-Assisted Therapy in PTSD, Calls for Additional Trial

Credit: US Food and Drug Administration

The US Food Drug Administration (FDA) issued a Complete Response Letter (CRL) for midomafetamine (MDMA) capsules for the treatment of posttraumatic stress disorder (PTSD).

Announced on August 09, 2024, by Lykos Therapeutics, the decision on MDMA-assisted therapy came after considerable negative feedback from the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC). On June 4, 2024, the committee voted 2 to 9 against MDMA-assisted therapy for PTSD, citing concerns about safety, cardiovascular risks, and issues related to functional unblinding in trial settings. According to the announcement from Lykos Therapeutics, the FDA has requested the company conduct an additional trial.^1,2,3

Despite the push for MDMA-assisted therapy even reaching the White House with members of the House and Senate, along with > 700 veterans, sending letters of support to President Joe Biden and FDA Commissioner Robert Califf, this was not enough to sway the FDA’s opinion on this treatment option.²

"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.¹ "While conducting another Phase 3 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’ application was based on 2 randomized, double-blind, placebo-controlled phase 3 trials (MAPP1 and MAPP2) evaluating MDMA-assisted therapy for PTSD. Findings revealed 68% of participants receiving MDMA-assisted therapy no longer met the criteria for PTSD.^1,2

Both trials achieved their primary endpoint, which was significant improvements in PTSD symptoms compared to solely traditional psychotherapy, as measured by the Clinician-Administered PTSD Scale for DSM-5. Additionally, the trials met their secondary endpoint by showing improvements in functional impairment associated with PTSD, measured by changes from baseline on the Sheehan Disability Scale.^1,2

Ahead of the decision, Lykos Therapeutics announced on August 1, 2024, new initiatives and measures for additional oversight for MDMA-assisted therapy to treat PTSD.³

The company had planned on establishing an independent advisory board with experts in corporate and medical ethics, innovation, psychiatry, and military and veteran health. Lykos Therapeutics also intended to work with top behavioral health facilities and collaborate on training.^2,3

Clinicians have recognized the unmet need in the PTSD space. For years, patients with PTSD only had 2 FDA-approved pharmacotherapy options: sertraline (Zoloft) and paroxetine (Paxil). However, up to 60% of people with PTSD do not respond to these treatment options.²

With the FDA not approving MDMA-assisted therapy, the question remains: what are the next steps for psychedelic research in the medical space?

“If the FDA were to delay its approval or even decide to reject it, it would be a setback for the field,” Casey A. Paleos, MD, the chief medical officer of InnerMost PBC, told HCPLive before the decision.³ “However, the data on its efficacy are too strong and convincing for that to be likely. I believe it's now a question of when, not if, and under what circumstances.”

References:

1. Lykos Therapeutics. Lykos Therapeutics Announces Complete Response Letter for Midomafetamine capsules for PTSD. Lykos Therapeutics - News Release Archive. August 9, 2024. Accessed August 9, 2024. https://news.lykospbc.com/2024-08-09-Lykos-Therapeutics-Announces-Complete-Response-Letter-for-Midomafetamine-Capsules-for-PTSD.
2. Derman, C. Leading Experts Discuss FDA's Pending Decision on MDMA-Assisted Therapy for PTSD. HCPLive. August 7, 2024. https://www.hcplive.com/view/leading-experts-discuss-fda-s-pending-decision-on-mdma-assisted-therapy-for-ptsd. Accessed August 7, 2024.
3. Lykos Therapeutics Announces New Initiatives and Measures for Additional Oversight for Midomafetamine-Assisted Therapy, if FDA Approved. Lykos Therapeutics. August 1, 2024. https://news.lykospbc.com/2024-08-01-Lykos-Therapeutics-Announces-New-Initiatives-and-Measures-for-Additional-Oversight-for-Midomafetamine-Assisted-Therapy,-if-FDA-Approved. Accessed August 7, 2024.