Updated August 9, 2024 at 7:11 p.m. ET

On Friday, drugmaker Lykos Therapeutics withdrew notified from the Food and Drug Administration that the agency has decided not to approve MDMA-assisted treatment for PTSD at this time. Instead, the agency asked the drugmaker to further study the safety and effectiveness of the treatment.

The long-awaited announcement came in the form of a “complete response letter” from the FDA to Lykos, according to a press release from the company.

It represents a significant setback for the company and the broader movement to bring psychedelics into the mainstream of mental health.

“It’s a big blow to the field,” says Dr. Boris Heifetsan 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.

Lyko CEO Amy Emerson called the FDA’s request for another Phase 3 study “deeply disappointing” and said conducting the study “would take several years.”

She added that many of the agency’s requests “can be addressed with existing data, post-approval requirements or by reference to the scientific literature.”

The treatment had received great support from patients, leaders in the field of mental health and psychedelics, and politicians from both parties. The past few weeks, advocates exerted great pressure from the public campaign, which emphasizes the urgent need for new and effective treatments for veterans and the millions of people affected by PTSD.

Many in the psychedelic industry had seen this as a defining moment. The FDA decision on MDMA can be seen as a wake-up call for other drugs in the pipeline such as psilocybin and LSD, both of which are considered “classic psychedelics” unlike MDMA.

But Dr. Mason Marks believes the FDA’s decision does not pose a problem for the broader field because the agency has repeatedly signaled it is 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 Center.

“I don’t think there’s any sign that development is going to slow down. If anything, it may intensify because the other companies might see an opportunity to really get in there and compete,” he says.

The wave of enthusiasm surrounding MDMA’s therapeutic potential has come from researchers 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,” the Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the high number of veteran suicides, said in a statement. “This is the epitome of bureaucratic red tape – and the result is that people will continue to die.”

Opposition to Lyko’s application had gathered momentum in recent months, culminating in a controversial public meeting when advisers to the FDA voted against the evidence support the treatment, largely based on concerns about flaws in the clinical research.

In his press release, Lykos said the FDA reiterated the issues raised by the committee.

The committee’s downvote put the FDA in a tricky spot, given that it has historically sided with the advisers.

“As discussed at the advisory committee meeting, there are significant limitations to the data 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 in an email.

“We will continue to encourage research and drug development that will advance innovation for psychedelic treatments and other therapies.”

Those hoping to see MDMA hit the market argue that concerns about the quality of the research were exaggerated and, in some cases, focused on study design problems that were not unique to MDMA.

The trials “undoubtedly had problems,” says Stanford’s Stapledbut the FDA could have addressed these concerns by approving the treatment with strict restrictions on how it is administered and a requirement to do a post-marketing study.

He worries that the decision to deny approval will stifle innovation and funding for other new treatments, including MDMA-like drugs being developed.

“The FDA has gone against the advice of advisory committees (in the past). It has approved drugs with potential for abuse,” Heifets said. “None of this is that radical, so I think they could have done something different here.”

On the other hand, Marks says that approval would have required the FDA to “stack on” so many restrictions because of concerns about Lykos’ application that it would ultimately have been “impractical” for the treatment to reach many people.

He also wonders if the all-out publicity blitz by Lykos and its allies was ultimately “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 that doesn’t mean they can’t succeed in the end.”

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 move forward with larger human trials and seek approval from federal regulators.

Lykos has up more than $100 million pending FDA approval of its MDMA treatment.

Optimism about the treatment stems in large part from the company’s promising Phase 3 clinical trials, which collectively enrolled about 200 people. The latest, published last year, showed roughly 70% of the participants no longer met diagnostic criteria for PTSD after three sessions of MDMA, compared with about 48% who had the same talk therapy protocol but received a placebo.

Follow-up research from the company showed that participants were still benefiting from the treatment at least six months after their last dosing session.

“While disappointing, this move by the FDA highlights the importance of conducting rigorous research into the safety and efficacy of MDMA-assisted therapy,” says Alan Davisdirector of the Center for Psychedelic Drug Research and Education at 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.”

The debate on the merits of Lyko’s application has become increasingly divided, with accusations that misconduct and bias in the clinical trials compromised the results and undermined its safety. The drug manufacturer and many of the therapists involved in the research have strongly denied these claims.

It is unclear to what extent any of this factored into the FDA’s consideration of the treatment.

In response to Friday’s decision, Emerson reiterated the company’s plan to push the research forward, saying it would “work tirelessly and use all available regulatory avenues to find a reasonable and expeditious path forward for patients.”

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