FDA panel rejects first MDMA treatment over concerns about trial failures

A panel of advisors to the Food and Drug Administration (FDA) on Tuesday declined to recommend approval of MDMA, commonly known as ecstasy or molly, as a treatment for post-traumatic stress disorder (PTSD). , which represents a severe setback for defenders of the inclusion of psychedelics in the treatment of mental disorders.

The agency's two votes by the agency's Advisory Committee on Psychopharmacological Drugs — one on the treatment's effectiveness and another on its safety — marked the first time FDA advisers have considered a Schedule I psychedelic for medical use. If approved, it would have been the first new treatment for PTSD in more than two decades.

The votes reflected panel members' struggle to find a balance between the need for new treatments for PTSD and serious concerns about data presented by drugmaker Lykos Pharmaceuticals that they said was flawed by inconsistencies, poor studies and accusations of misconduct.

“It seems like MDMA has had a positive impact on a lot of people, but there seem to be a lot of problems with the data,” said Melissa Decker Barone, an associate professor in the department of psychiatry at the University of Maryland School of Medicine.

Walter Dunn, an assistant clinical professor in the department of psychiatry at the University of California, Los Angeles, was the only one who voted “yes” on safety and one of two who voted “yes” on efficacy. Although he was concerned about the drug, he noted that “we urgently need treatments for PTSD.”

“There is no free lunch in medicine,” Dunn said. “What has potential benefits also has potential for harm.”

The panel's decision was based on the results of two Phase 3 clinical trials that included nearly 200 patients with moderate to severe PTSD. In both studies, experts found that a therapeutic approach of administering MDMA in three eight-hour therapy sessions, four weeks apart, worked better than a placebo in reducing the severity of symptoms. People also underwent a series of shorter talk therapy sessions before and after receiving the drug or placebo.

In the most recent trial, published last September, about 86% of participants who received MDMA treatment along with talk therapy experienced a reduction in symptom severity after 18 weeks. About 71% of participants who received the treatment met diagnostic criteria for PTSD, compared to 48% who also received therapy but took a placebo.

The vote came after an analysis by FDA scientists, released last week, raised questions about the way the trials were done.

A randomized, double-blind clinical trial is considered the standard for determining whether a drug works better than a placebo. “Double-blind” means that neither the patient nor the researcher administering the drug knows whether it is a placebo or the real drug.

In the MDMA trials, however, due to “profound alterations in mood, sensation, suggestibility, and cognition,” the vast majority of participants were able to guess exactly which treatment they had received after the study was completed, according to FDA scientists. “As a result, the studies are almost impossible to validate.”

This could “artificially inflate” the results, David Millis, an FDA official who oversaw Lykos' approval application, said during Tuesday's meeting, because participants may feel that the treatment works if they know they are taking the drug or, for that matter, On the contrary, it does not work if they are taking a placebo.

“We expressed concern about the adequacy of the trial,” he said.

Last week, the Institute for Clinical and Economic Review, a nonprofit group that evaluates drug costs, said that patients and providers in the trial treated psychedelics “more like a religious movement than pharmaceuticals.”

In fact, panel members had reservations about the trials, including that many patients had used MDMA before and that some therapists might have encouraged favorable patient reports.

“The data was promising, but given the 40% of people who had previously used MDMA, the limited information on recruitment and recruitment through referrals, I wonder to what extent this influenced the effectiveness,” said Elizabeth Joniak. Grant, a patient advocate and sociologist at the University of North Carolina at Chapel Hill.

Group members also expressed concern about potential risks to patients at the hands of providers, following allegations of sexual misconduct during a previous trial.

Lykos recommended the presence of two therapists in therapy sessions. Panel members wanted to ensure that both therapists were licensed and that patients' concerns were taken into account.

“We need a clear path to reporting,” said Kim Witczak, a consumer advocate and executive director of Woody Matters, a drug safety organization. “I have been involved in pharmaceutical safety issues for a long time and I hear from harmed patients all the time, and the reality is that patients report and nothing is done.”

The decision will now go to the FDA, which is expected to make a final ruling before August 11. The committee's vote is only a recommendation and the agency does not have to follow its advice, although it usually does.

According to the FDA, about 13 million Americans, many of them veterans, suffer from PTSD. This disorder, which develops in some people exposed to serious injury or violence, can be debilitating: people often experience intrusive memories and nightmares that can cause high levels of anxiety, suicidal thoughts, self-destructive behavior and sleep problems.

Talk therapy is the first line of treatment for this condition, either alone or in combination with one of two antidepressants, sertraline (Zoloft) or paroxetine (Paxil).

However, data presented by the agency at Tuesday's meeting revealed that patients often drop out of treatment with talk therapy alone. What's more, response rates to medications rarely exceed 60%, and fewer than 20% to 30% of PTSD patients achieve complete remission of their symptoms.

Researchers are still trying to understand exactly how MDMA helps PTSD patients, but the drug is thought to work by calming the brain's fear and anxiety response, according to David Olson, director of the Institute of Psychedelics and Neurotherapeutics at the University of Massachusetts. California in Davis.