On Friday, drugmaker Lykos Therapeutics received word from the Food and Drug Administration that the agency has decided not to approve MDMA-assisted therapy for PTSD at this time. Instead, the agency asked the drugmaker to further study the safety and efficacy of the treatment.
The heavily anticipated announcement came in the form of a “complete response letter” from the FDA to Lykos, according to a company press release.
It represents a significant setback for the company and the broader movement to bring psychedelics into the mainstream of mental health care.
“It’s a huge blow to the field,” says Dr. Boris Heifets, an anesthesiologist at Stanford University whose lab studies psychedelics.
Lykos said it plans to request a meeting with the FDA to ask for reconsideration of the decision.
Lykos’ CEO Amy Emerson called the FDA’s request for another phase 3 trial “deeply disappointing,” and said conducting the study “would take several years.”
She added that many of the requests from the agency “can be 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 from both parties. In recent weeks, advocates mounted a major public pressure campaign, emphasizing 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. The FDA decision on MDMA could be seen as a bellwether for other drugs that are 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 signaled repeatedly it’s open to psychedelic research.
“I think this is a unique case,” says Marks, a law professor and senior fellow with the Project on Psychedelics Law and Regulation at Harvard Law School's Petrie-Flom Center.
“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,” he says.
The wave of enthusiasm around MDMA's therapeutic potential has come from research scientists at top academic centers and even the Department of Veterans Affairs.
Supporters of the drug were dismayed by Friday's decision.
“The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization 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 advisors to the FDA voted against the evidence backing the treatment, largely based on concerns about shortcomings in the clinical research.
In its press release, Lykos said the FDA echoed the issues raised by the committee.
The committee's downvote put the FDA in a tricky spot, given that it historically sides with the advisors.
“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 said to NPR in an email.
“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,” says Stanford's Heifets, but the FDA could have dealt with those concerns by approving the treatment with strict restrictions around how it’s administered and a requirement to do a post-market study.
He worries the decision to deny approval will stifle innovation and funding into other novel treatments, including MDMA-like drugs that are being developed.
“The FDA has gone against advisory committee advice [in the past]. It has approved drugs with abuse potential,” says Heifets. “None of this is that radical, so I think they could have done something else here.”
On the other hand, Marks says that approval would have required the FDA to “pile on” so many restrictions because of concerns about the Lykos’ application that ultimately it would have been “impractical” for the treatment to reach many people.
He also wonders whether the all-out publicity blitz by Lykos and its allies was, in the end, “counterproductive” because it put the FDA in an awkward position by making the decision so politicized.
“This is not the end of the road for Lykos,” he says, “It will cost them financially, but it doesn’t mean they can’t ultimately succeed.”
The push to establish MDMA-assisted therapy as a legitimate treatment for PTSD stretches back two decades.
Researchers affiliated with the nonprofit 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 $100 million 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 together enrolled about 200 people. The most recent one, published last year, showed just over 70% of participants no longer met the diagnostics criteria for PTSD after three therapy sessions with MDMA, compared to 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, this move by the FDA highlights the importance of conducting rigorous research into the safety and efficacy of MDMA-assisted therapy,” says Alan Davis, director of the Center for Psychedelic Drug Research and Education at the Ohio State University, “Despite this setback, I am hopeful that there will be a better outcome down the road 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 its safety. The drugmaker and many of the therapists involved in the research have steadfastly denied those claims.
It’s unclear to what extent any of this factored into the FDA’s deliberation on the therapy.
In response to Friday’s 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 ahead of MDMA.
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