The US Food & Drug Administration has refused approval for mind-altering MDMA-assisted therapy, recommending instead that American drugmaker Lykos Therapeutics carry out further studies on the safety and efficacy of the treatment.
In June, the FDA’s advisers voted against the therapy based on the drug “ecstasy” for patients with post-traumatic stress disorder, saying the benefits did not outweigh the risk. The agency is not required to follow the panel’s advice, but usually does so, and there had been tense anticipation until its final decision this week.
The announcement came in the form of a “complete response letter” to Lykos, which said the decision represents a significant setback for the company and the broader movement to bring psychedelics into the mainstream of mental healthcare.
“It’s a huge blow to the field,” Dr Boris Heifets, an anaesthesiologist at Stanford University whose lab studies psychedelics, told NPR.
Lykos plans to request a meeting with the FDA to ask for reconsideration of the decision, according to company CEO Amy Emerson, who called the FDA’s request for another phase 3 trial “deeply disappointing”, and saying that conducting the study “would take several years”.
She added that many of the requests from the agency could have been addressed “with existing data, post-approval requirements or through reference to the scientific literature”.
The treatment had garnered considerable support from patients, leaders in the field of mental health and psychedelics, and politicians.
In recent weeks, advocates had mounted a major public pressure campaign, emphasising the dire need for new and effective treatments for veterans and the millions of people affected by PTSD.
Many in the psychedelics industry had viewed this as a pivotal moment, a bellwether for other drugs in the pipeline like psilocybin and LSD, which are both considered “classic psychedelics”, unlike MDMA.
But Dr Mason Marks believes the FDA’s decision doesn’t spell trouble for the broader field because the agency has repeatedly indicated that it’s open to psychedelic research.
“I think this is a unique case,” said Marks, a law professor and senior fellow with the Project on Psychedelics Law and Regulation at Harvard Law School’s Petrie-Flom Centre.
“I don’t think there’s any sign that progress is going to be slowed. If anything, it might intensify because the other companies might see an opportunity to really get in there and compete.”
Supporters of the drug were dismayed by the decision.
“The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans’ organisation that had lobbied for FDA approval, citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape – and the result is people will keep dying.”
Opposition to the Lykos’ application had gained momentum in recent months, culminating in a contentious public meeting when advisers to the FDA voted against the evidence backing the treatment, largely based on concerns about shortcomings in the clinical research.
Lykos said the rejection letter from the FDA echoed the issues raised by the committee.
“As discussed at the advisory committee meeting, there are significant limitations to the data contained in the application that prevent the agency from concluding that this drug is safe and effective for the proposed indication,” an FDA spokesperson told NPR.
“We will continue to encourage research and drug development that will further innovation for psychedelic treatments and other therapies.”
Those hoping to see MDMA make it to market argue that concerns about the quality of the research were overblown and, in some cases, focused on issues with the study design that weren’t unique to MDMA.
The trials “undoubtedly had problems”, said Stanford’s Heifets, but the FDA could have dealt with those concerns by approving the treatment with strict restrictions around how it is administered, and a requirement to do a post-market study.
On the other hand, he said approval would have required the FDA to “pile on” so many restrictions because of concerns that ultimately, it would have been “impractical” for the treatment to reach many people.
The push to establish MDMA-assisted therapy as a legitimate treatment for PTSD stretches back two decades.
Researchers affiliated with the non-profit Multidisciplinary Association for Psychedelic Studies, or MAPS, pioneered the early studies and developed the therapy protocol embedded in the treatment.
That work ultimately set the stage for the drugmaker, which was incubated by MAPS, to press forward with larger human trials and seek approval from federal regulators.
Lykos has raised more than $100m in anticipation of FDA approval of its MDMA therapy.
Optimism around the treatment largely stems from the company’s promising phase 3 clinical trials, which in total, enrolled about 200 people. The most recent one, published last year, showed just more than 70% of participants no longer met the diagnostics criteria for PTSD after three therapy sessions with MDMA, compared with about 48% who had the same talk therapy protocol but took a placebo.
Follow-up research from the company showed participants were still benefiting from the treatment at least half a year after their last dosing session.
“Although disappointing, the FDA decision highlights the importance of conducting rigorous research into the safety and efficacy of MDMA-assisted therapy,” said Alan Davis, director of the Centre for Psychedelic Drug Research and Education at Ohio State University.
“Despite this setback, I am hopeful that there will be a better after more research is completed in the coming years.”
Debate over the merits of the Lykos application has become increasingly divisive, with allegations that misconduct and bias in the clinical trials compromised the findings and undermined safety.
The drugmaker and many of the therapists involved in the research have continued to deny those claims, and it’s unclear to what extent any of this factored into the FDA’s deliberation on the therapy.
In response to the decision, Emerson reiterated the company’s plan to push the research forward, saying they’d “work tirelessly and use all available regulatory pathways to find a reasonable and expeditious path forward for patients”.
Given what’s required to conduct another trial, Heifets believes psilocybin is now poised to gain approval before MDMA.
NPR article – FDA gives thumbs down to MDMA for now, demanding further research (Open access)
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FDA says no to ecstasy for PTSD treatment
Ecstasy approval for PTSD likely after large trial