FDA declines to approve novel MDMA therapy to treat PTSD, with request for more trial data

The US Food and Drug Administration has declined to approve an application for the use of MDMA, commonly known as ecstasy, as a treatment for post-traumatic stress disorder, according to a news release from drug sponsor Lykos Therapeutics. The company says the agency has requested an “additional Phase 3 trial to further study the safety and efficacy” of the treatment.

The initial application from Lykos presented positive data from two late-stage clinical trials that used MDMA in combination with talk therapy to treat PTSD. About 200 people participated in the Lykos trials, with a treatment program that involved three eight-hour sessions in which they took MDMA in the presence of two therapists. The MDMA sessions were spaced about a month apart, along with additional talk therapy sessions.

MDMA is an entactogen, a class of psychoactive drugs that produce experiences of emotional communion, relatedness and emotional openness.

This is the first time the FDA has considered a psychedelic drug for medical use. The novel treatment has the potential to transform a field with significant need, but the review process has also raised questions about how it should be used in a clinical setting. MDMA is currently classified as a Schedule I drug under the Controlled Substances Act, or a prohibited substance that has “no currently accepted medical use and a high potential for abuse.” Reclassifying the drug to a lower level would be a marked shift involving multiple federal agencies.

In June, an independent FDA advisory committee voted overwhelmingly against the treatment, citing concerns about the integrity of the particular trials up for review. When reviewing the trial data from Lykos Therapeutics, many of the committee members applauded the exploration of this line of treatment and lauded the potential it holds but raised critical doubts – notably regarding missing information about safety and bias in efficacy data. They said it was also difficult to parse how much the accompanying talk therapy contributed to outcomes, which is an area that the FDA does not regulate.

“Participants appear to experience rapid, clinically meaningful, durable improvement in their PTSD symptoms,” the FDA wrote in a briefing document about the studies before the committee meeting.

In addition to blurry data on efficacy, there were concerns about safety data, the FDA said at the time.

MDMA is known to have potential for abuse, but the FDA cautioned that the research did not appropriately assess this as an adverse event in the context of the treatment program.

Reports from illicit use of MDMA suggest that it may pose risks to both heart and liver health. The phase III clinical trials showed “significant increases in both blood pressure and pulse” among participants, the FDA said, but certain related assessments were incomplete. And liver health was assessed only in small groups from earlier phases of the clinical trials.

Lykos said Friday that conducting the additional trial could take years but that it remains confident that the concerns raised by the FDA and its advisers can be addressed. Lykos says it plans to seek a meeting with the agency to discuss its recommendations and ask it to reconsider.

“Lykos will work diligently in the coming months to address FDA’s concerns and to take advantage of agency processes to resolve scientific disagreements,” the company said in Friday’s news release. “Following the FDA meeting, Lykos expects to provide an update on next steps for the resubmission.”

About 5% of adults in the United States – about 13 million people – experience PTSD in any given year, according estimates from the National Center for PTSD. But current treatment options, including antidepressants and some specialized forms of cognitive behavioral therapy, are limited in their scope and effectiveness, with few alternatives available to help those who don’t respond well to them.

The nonprofit consumer advocacy group Public Citizen, which testified before the FDA advisory committee in June to ask that the treatment not be approved, applauded Friday’s decision.

“Although psychedelic drugs are a promising approach to mental health care, FDA approval of a new drug should always be based on rigorous evidence of safety and effectiveness,” Dr. Robert Steinbrook, director of Public Citizen’s Health Research Group, said in a statement. “By declining to approve MDMA, the FDA will encourage the company as well as other researchers studying psychedelic drugs to conduct better clinical trials.”

But some veterans groups said they were “incredibly disappointed” by the FDA decision.

“It is hard to see how the FDA’s decision can be justified when it has plenty of tools to ensure a slow, cautious roll-out of this novel treatment, which could have at least been conditionally approved with required safety data collection and post-marketing studies, as well as a more restrictive risk mitigation strategy,” Martin Steele, president of the Veteran Mental Health Leadership Coalition, and Reason for Hope Executive Director Brett Waters said in a statement. “Instead, Veterans will continue to be forced to leave the country or to seek underground providers for MDMA-AT or other psychedelic therapies, which is a tragic and unconscionable outcome.

“While we remain confident MDMA-AT will eventually be approved, there is no doubt that this decision will lead to more unnecessary suffering and lives lost.”