The Food and Drug Administration has rejected a high-profile application for MDMA-assisted therapy to treat PTSD, citing insufficient data to support either safety or efficacy. The agency instructed applicant Lykos Therapeutics to redo its controversial Phase 3 trial and then resubmit the application. The company announced the news August 9, stating it will ask the FDA to reconsider.
Lykos, formerly known as the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation, is a for-profit pharmaceutical company focused on bringing new mental health treatments to market. The company’s MDMA research led to the FDA’s first formal consideration of a Schedule I psychedelic drug for approval as a medical treatment.
Lykos’ new drug application involved the company’s MDMA capsules, designed to be used during therapy sessions overseen by two trained facilitators, as studied in the Phase 3 trial. The FDA ultimately issued a “complete response letter,” meaning it described specific problems and how Lykos can attempt to remedy them and apply again.
“The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones,” Lykos Chief Executive Officer Amy Emerson stated August 9.
“While conducting another Phase 3 study would take several years,” Emerson continued, “we still maintain that many of the requests that had been previously discussed with the FDA and raised at the Advisory Committee meeting can be addressed with existing data, post-approval requirements or through reference to the scientific literature.”
With a substance like MDMA, study participants can often tell whether or not they received a placebo.
On June 4, an FDA advisory committee had recommended against approving the application. Some of the concerns prompted by the Lykos Phase 3 trial focused on consent, following a participant’s allegations of sexual assault by facilitators. This intersected concerns about how to balance appropriate training—clinical MDMA sessions often incorporate physical touch—with keeping the treatment affordable for as many patients as possible. There’s no guarantee insurers would cover the sessions, and some estimates for out-of-pocket costs exceed $10,000 per patient.
Another major concern highlighted by the advisory committee was the difficulty in keeping the Phase 3 double-blinded trial unbiased. With a substance like MDMA, participants can often tell whether or not they received a placebo.
“I do think we need a different regulating body to oversee this,” Dr. Genesee Herzberg, a licensed psychologist who was involved in the Phase 3 Lykos trial told Filter ahead of the FDA verdict. She specializes in trauma work and has trained to provide MDMA-assisted therapy for PTSD specifically. “There are so many psychedelic training programs out there and they’re not standardized at all. We need to really get clear on what needs to be incorporated in training, and what credentialing a psychedelic therapist looks like.”
The lead-up to the August 11 deadline for the FDA to issue its decision was marked by a substantial bipartisan push for the agency to go against the advisory committee’s recommendation.
One day after the FDA delivered its verdict, the journal Psychopharmacology retracted three MDMA involving Lykos-affiliated researchers.
Veterans advocacy groups like Healing Breakthrough, which collaborated with Lykos on the trials, held near-constant meetings with legislators. In a letter to FDA Commissioner Robert Califf, 19 senators emphasized the veteran suicide crisis and stated that, should the evidence bear out, “it is our responsibility to ensure that this treatment option is made available to those who could benefit.” A letter signed by 61 House representatives urged President Biden to support the application for the same reasons and warned against listening to outside interest groups.
“It is not our intent to urge the FDA in any direction related to its decision, which must be based solely on the data and evidence,” stated the August 2 letter to Biden. “However, we are aware that … certain groups and individuals have voiced criticism of the application. It is our understanding that while these critics may be well-intentioned, their criticism is not necessarily reflective of the science, but rather their personal ideological beliefs and biases.”
On August 10, one day after Lykos announced the FDA decision, the journal Psychopharmacology retracted a study analyzing Lykos’ Phase 2 research; another study analyzing long-term followup of that research; and a third MDMA study also affiliated with Lykos. The retraction notes on all three cite “protocol violations amounting to unethical conduct” and allege that the authors had knowingly concealed the violations.
The only other MDMA study currently recruiting for Phase 3 trials is also affiliated with Lykos. Multiple studies on psilocybin, the psychedelic compound in certain mushrooms, are currently recruiting for Phase 3, most of them focused on depression. The FDA has not approved any new treatments for PTSD since 1999.
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