The U.S. Food and Drug Administration (FDA) has not approved the combination of the hallucinogen midaphetamine and adjunctive therapy (MDMA-AT) for the treatment of depression. Post-traumatic stress disorder (PTSD).
Drug maker Lycos Therapeutics said in a statement that the agency had issued a full response, determined the treatment “cannot be approved based on the data submitted to date” and requested further studies.
“The FDA has requested that Lycos conduct additional Phase 3 trials to further study the safety and effectiveness of midaphetamine. Lycos has requested a meeting with the FDA to seek reconsideration of this decision and to further discuss the agency’s recommendation regarding its resubmission for regulatory approval of midaphetamine capsules,” the statement said.
The decision came after an FDA advisory committee overwhelmingly voted against approval, saying there was insufficient evidence of effectiveness and that the benefits of the treatment did not outweigh the risks.
MDMA-AT would have been the first hallucinogen-based treatment approved by the FDA for any condition in the United States and the first approved PTSD treatment in 24 years.
The rejection is a blow to drug company Lycos Therapeutics, which had sought approval of the treatment based on two pivotal trials that were plagued by criticism of potential unblinding and investigator bias.
A campaign by veterans groups had been urging officials in recent weeks to overrule the advisory committee’s recommendation and approve the treatment, and this week a bipartisan group of about 80 lawmakers voted to approve it. I sent a letter He called on President Joe Biden to support treatment.
“The FDA’s request for new studies is deeply disappointing not only for all those who have dedicated their lives to this pioneering work, but also for the millions of Americans with PTSD and their families who have not found new treatment options in more than 20 years,” Lycos Therapeutics CEO Amy Emerson said in a statement. “While Phase 3 studies take several years to conduct, we still believe that many of the requests raised in previous discussions with the FDA and advisory committees can be addressed through existing data, post-approval requirements or references to the scientific literature.”
Approximately 13 million adults in the U.S. suffer from PTSD. About 7% of all veterans will experience PTSD in their lifetime (compared to 6% of the general population), but for some military personnel, the rate is reported to be as high as 29%.
Ahead of an FDA advisory committee hearing in June, several veterans groups had submitted public comments in support of the treatment, and leaders of the U.S. Department of Veterans Affairs had been full on with the promise of psychedelics in treating PTSD.
MDMA-AT was originally developed by the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS), which in 2014 formed a subsidiary of its Public Benefit Corporation (MAPS PBC), which then separated completely from MAPS to become Lykos in 2024.
The FDA granted MDMA-AT breakthrough therapy designation in 2017 and put it on the fast track to approval.
As previously reported Medscape Medical NewsResearchers presented and published data from the company’s first clinical trial of this treatment, MAPP1, in 2021.
In the study, 90 patients with PTSD were randomly assigned to receive either 80 mg or 120 mg of MDMA or a placebo, and then evaluated during three integrative psychotherapy sessions lasting a total of eight hours.
Patients can receive additional doses of MDMA after the initial dose, and the company says 82% of patients report significant improvement, with more than half saying their PTSD is gone.
Eleven patients (12%) experienced a recurrence within 12 months. Medscape Medical News A second trial, MAPP2, reported similar results in 104 patients.
But in June, the FDA’s Psychotropic Drugs Advisory Committee voted 11-2 that the efficacy data was not compelling, with only one committee member agreeing that the benefits outweigh the risks.
The reviewers cited potential bias due to participants’ previous MDMA use, claims of unreported adverse events, a lack of data on the drug’s potential for misuse, and at least one documented case of Sexual assault Currently in Phase 2 research.
All committee members had concerns about “functional unblinding” in both trials: Most patients, and even therapists, knew who had received the active treatment, which could have biased the results, they said.
As previously reported Medscape Medical NewsConcerns were also raised about the design of the clinical trials, a citizen petition calling on the FDA to investigate possible ethics violations, and complaints from former employees.
To address some of the FDA committee’s concerns, Lycos Announces The company said last week that it would take steps to ensure additional oversight of MDMA-AT if the FDA approves it for the treatment.
This includes creating an independent advisory board of outside experts to guide the commercial launch. MDMA-AT will only be available at behavioral health centers that meet FDA and Drug Enforcement Administration requirements. Lycos has also committed to working with other institutions on training on how to administer the treatment.
Alicia Ault is a freelance journalist based in St. Petersburg, Florida, whose work has appeared in publications such as: JAMA and Smithsonian.com. You can find her at X @aliciaault.
Kelli Whitlock Burton is associate editor of Medscape Medical News.
