FDA rejects MDMA therapy for treatment of PTSD. What’s next?

WASHINGTON – MDMA came close to becoming medicine on Friday, but it missed the mark.

The Food and Drug Administration declined to approve what would have been the first psychedelic drug used for the treatment of post-traumatic stress disorder, a blow to advocates who have touted the potential of the Schedule I controlled substance also known as ecstasy to treat mental health disorders.

The FDA was considering an application for a treatment manufactured by the California-based biotech Lykos Therapeutics that involves intense psychotherapy sessions administered to the patient in conjunction with MDMA. The idea is that MDMA, in combination with psychotherapy, can help patients access parts of their memory for deeper healing.

The agency is asking Lykos to complete an additional Phase 3 study to further demonstrate safety and efficacy. Lykos said in a statement that it plans to request a meeting with the FDA to ask them to reconsider the decision.

Lykos, among other researchers and biotechs, is aiming to prove that psychedelic drugs have medical potential. Its approval would mark a significant shift in how the government approaches psychedelics, which have been federally banned since the 1970s.

“While conducting another Phase 3 study would take several years, 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,” Lykos CEO Amy Emerson said in a statement Friday.

Issues with the trial

Friday’s rejection follows an advisory panel meeting earlier this year, during which the FDA’s independent experts overwhelmingly agreed that it was not clear whether the benefits of the treatment outweighed the risks.

A main roadblock? It was pretty easy for trial participants to tell that they were on ecstasy.

Placebo-controlled trials are the gold standard for new medications, but the advisory committee raised issues with placebo bias in the trial, an issue that’s also been raised with approvals for drugs like opioids and antidepressants.

The panel also questioned a lack of diversity among participants and the addictive potential of the drug.

Lykos responded by assembling an independent advisory board to guide the company on the commercial launch of the medication, and providing training to health care providers.

Aron Tendler, the chief medical officer at the mental health care company GrayMatters Health underscored in an interview Thursday that Lykos’ study was peer reviewed and produced evidence that it worked for participants – but it didn’t answer several key questions.

He emphasized that the psychotherapy portion of the treatment is nearly 40 hours total which makes it difficult to discern how much work the MDMA is actually doing.

He also pointed out that under Lykos’ model, the therapy allows for the psychotherapist to physically touch the patient, which differs from standard psychiatric care.

“The question is really, how much of this result is related to the drug? How much of the result is related to the therapy? How much of the result is related to people believing they’re getting it?” he said.

Outside pressure

The FDA was up against pressure from lawmakers and lobbyists alike to greenlight the therapy.

More than 80 lawmakers in the House and Senate had sent letters to FDA Commissioner Robert Califf last week strongly suggesting that the agency should approve the drug, citing high rates of suicide among veterans with the condition.

“Despite billions of federal dollars spent on addressing PTSD and mental health, the number of Veteran lives lost to suicide has not decreased,” the lawmakers wrote. “This is due in part to the fact that the FDA has not approved any new treatments for PTSD in nearly 25 years. This astounding lack of innovation has undoubtedly contributed to our rising Veteran suicide rates over the past two decades.”

Some experts said lawmakers are being heavy-handed with Lykos’ case.

Holly Fernandez-Lynch, a professor of medical ethics at the University of Pennsylvania, acknowledged in an interview Tuesday that the FDA often has to make value-based decisions when data isn’t clear.

Still, she said lawmakers’ input in this particular decision went too far.

“It’s important to have some checks and balances for the political process to be able to influence FDA,” she said. “However, if we have the political process dictating what specific drugs get approved, then I’m not going to feel confident that they’re getting approved based on the science.”

The topic has been a bright spot for bipartisan collaboration over the past year, however, as it has been pushed as a solution for military veterans who are out of options to treat PTSD.

Reps. Alexandria Ocasio-Cortez, D-N.Y., and Daniel Crenshaw, R-Texas, banded together last summer to sponsor a bill that was eventually enacted as part of the fiscal 2024 National Defense Authorization Act (HR 2670), which directed the Department of Defense to fund research on the potential for psychedelics to be used to treat PTSD and traumatic brain injuries in service members.

Looking ahead

Ferndandez-Lynch said the rejection is disappointing for advocates who are encouraged by the drug’s potential, but said research is unlikely to stop.

“It’s not, ‘Oh my god, this can’t be done,’ ” she said. “It’s ‘Well, Lykos made some important misjudgments, and those are fixable misjudgments.’ ”

Tendler also pointed to other nonpsychedelic PTSD treatments that have gained some traction over the years, highlighting a device developed by GrayMatters that the FDA cleared last year to treat PTSD.

“I don’t think psychedelics are going away, even if this is rejected,” he said. “Just because this wasn’t done the best way, it doesn’t mean that there is a real roadblock that people are forgetting about.”