The FDA's Psychopharmacologic Drugs Advisory Committee recommended against the approval of midomafetamine for treating posttraumatic stress disorder, a novel approach that combines pharmacological intervention and psychotherapy. The vote was overwhelmingly against, with 10 members voting "no" and only 1 member voting "yes."
The FDA convened the advisory committee to evaluate the efficacy and safety data submitted by Lykos Therapeutics. The data included results from two pivotal Phase 3 clinical trials, MAPP1 and MAPP2, which demonstrated that midomafetamine (MDMA), administered in conjunction with psychological support, resulted in rapid, clinically meaningful, and durable improvements in posttraumatic stress disorder (PTSD) symptoms. The studies involved patients with severe and moderate-to-severe PTSD. Significant reductions in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity scores compared to placebo were observed.
Despite these results, the advisory committee raised concerns over functional unblinding, where patients and investigators could deduce the treatment due to the drug's effects. Additionally, issues regarding the long-term safety and potential for abuse of MDMA were emphasized. The committee ultimately concluded that the potential risks of MDMA outweighed its benefits.
The panel also questioned the adequacy of the proposed Risk Evaluation and Mitigation Strategy (REMS) to monitor and mitigate risks associated with MDMA, such as cardiovascular events and potential abuse. They found the REMS plan proposed by Lykos Therapeutics, which included comprehensive monitoring protocols to ensure patient safety during and after treatment sessions, insufficient to address these concerns.
Before the vote, in an open letter to the FDA, researchers from the Psychedelic Therapy Research at the Icahn School of Medicine at Mount Sinai in New York, NY wrote, "Our clinical experience in our current trial leads us to fully support the approval of midomafetamine capsules used in combination with psychotherapy for the treatment of posttraumatic stress disorder. Our patients report that this treatment has been life-changing, leading to disease remission and drastically improved quality of life."
The American Psychiatric Association voiced public safety concerns noting, "It is crucial to prioritize patient safety and public health, ensuring that any new treatment for PTSD does not inadvertently lead to adverse consequences for individuals and society as a whole."
Raymond C. Turpin, Psy.D., of the Pearl Psychedelic Institute in Waynesville, NC, was involved in an expanded access program. He reported in a letter to the FDA that the four patients in the institute's program (aged 50 or older) with PTSD for 31-60 years had given up hope. However, after following the MDMA-assisted therapy program for five months, the patients no longer had a DSM-5 PTSD diagnosis.
There are currently 22 veterans committing suicide daily in the U.S., noted Turpin. "As a clinician practicing in southern Appalachia, I see midomafetamine-assisted therapy as a potential gamechanger in the prevention of the intergenerational transmission of trauma and PTSD."
The Institute for Clinical and Economic Review (ICER) was critical of an approval based on the unblinding nature of the research. "We have substantial concerns about the validity of the results. Because of the effects of MDMA, the trials were, essentially, unblinded with nearly all patients who received MDMA correctly identifying that they were in the MDMA arm of the trials," they wrote in a draft evidence report.
Mr. Turpin objected noting the concerns of the ICER are "some of the tired old criticisms from the 1960s about psychedelic compounds not being well-suited for double-blind research."
If the FDA follows the committee's recommendation, MDMA will not be approved as a psychedelic-assisted therapy for PTSD, leaving millions of patients still searching for effective treatment options.