Landmark meeting weighs MDMA-assisted therapy using the party drug, also known as ecstasy or molly, as a treatment for post-traumatic stress
A panel of independent advisers to the Food and Drug Administration on Tuesday cast doubt on the benefits of MDMA-assisted therapy for post-traumatic stress disorder, marking a pivotal moment for the booming field of psychedelic medicine.
The effort by privately held Lykos Therapeutics to win FDA approval for its MDMA therapy has triggered a barrage of questions from regulators, psychiatrists and independent researchers about clinical trials of the therapy and the reliability of data on the treatment's safety and efficacy.
One key issue: Due to the intense effects of MDMA, trial participants and researchers may have a strong sense of which patients received the active drug versus the placebo, opening the door to bias that could influence the trial outcomes, experts say.
In votes taken late Tuesday, the majority of the FDA advisory panel's members said the available data do not show the drug is effective in patients with PTSD and that the benefits of the treatment - even with a proposed FDA drug-safety program in place - would not outweigh its risks.
The FDA does not have to follow advisory-committee recommendations, but it often does. The agency's decision on the application is expected by mid-August.
MDMA is a stimulant and hallucinogen, widely known as a party drug called ecstasy or molly. But like some other psychedelic drugs, MDMA is also increasingly recognized for its therapeutic potential. The FDA in February granted priority review to Lykos's new drug application for MDMA in combination with talk therapy for treatment of PTSD.
The meeting Tuesday comes amid a surge in interest in - and debate over - psychedelic drugs as potential mental-health treatments. Ketamine, an anesthetic, is increasingly being used as a mental-health treatment, although it has not been approved for that use by the FDA. The agency also recently granted a breakthrough-therapy designation to Mind Medicine Inc.'s (MNMD) LSD-based treatment for generalized anxiety disorder. And Compass Pathways PLC (CMPS) is studying the hallucinogen psilocybin as a treatment for depression and other conditions.
Lykos, previously known as MAPS Public Benefit Corp., said in January that it had raised more than $100 million in an oversubscribed Series A financing round.
But questions about the value of the MDMA-assisted therapy for PTSD intensified in the weeks leading up to Tuesday's meeting. The Institute for Clinical and Economic Review, an independent, nonprofit research group that studies drugs' effectiveness and value, said in mid-May that there was not enough evidence to assess the risk-benefit tradeoffs of the MDMA-assisted therapy and that it could not evaluate the extent to which bias influenced the reporting of benefits in the clinical trials.
"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," ICER said in its report. "This would always raise concerns about bias, but these concerns are particularly heightened as we heard from multiple experts about the very strong prior beliefs of those involved in the trials (as investigators, therapists, and patients) about the benefits" of MDMA-assisted therapy, ICER wrote.
"We stand by the quality and integrity of our research and development program," Lykos CEO Amy Emerson said in a statement. "We are confident in the FDA's robust evaluation process, and we will continue to collaborate and answer any remaining questions" from the agency in advance of the regulatory decision, Emerson said.
Lykos also said in a briefing document prepared for the FDA meeting that it had taken several steps to minimize the impact of "functional unblinding," or patients and researchers potentially knowing who received MDMA versus a placebo. Among other measures, independent raters' interviews with the trial participants were structured to avoid discussion of participants' experience during the treatment period, Lykos said.
The FDA also raised questions about the treatment's safety in a briefing document prepared for Tuesday's meeting, noting significant increases in blood pressure and pulse among some trial participants as well as the potential for abuse of MDMA. If MDMA is approved, a drug-safety program called a Risk Evaluation and Mitigation Strategy will be necessary to ensure the benefits outweigh the risks of serious harm, the FDA said.
If Lykos wins FDA approval, Emerson said in the statement, "we will be planning for a responsible introduction of this new treatment into the healthcare system with careful consideration of its potential benefits and risks, in accordance with established medical guidelines, protocols, and quality standards."
While there is debate about Lykos's bid for regulatory approval of MDMA-assisted therapy, there's broad agreement about the need for new treatments for PTSD, which affects about 13 million people in the U.S. Selective serotonin reuptake inhibitors are often used to treat PTSD, but patient response rates rarely exceed 60%, and fewer than 20% to 30% of patients achieve full remission, the FDA said in its briefing document.
https://www.morningstar.com/news/marketwatch/20240604759/ecstasy-as-a-ptsd-treatment-gets-thumbs-down-from-fda-advisers
