Lykos Therapeutics’ attempt to get the first ever MDMA treatment approved in post-traumatic stress disorder suffered a crushing blow yesterday when an FDA advisory committee voted against recommending approval.
While the FDA does not have to follow the committee’s advice, it typically does.
The Psychopharmacologic Drugs Advisory Committee voted no on both questions. The first asked whether the available data showed that Lykos’ midomafetamine (MDMA) therapy is effective in patients with PTSD. The committee voted 9-2 against the treatment. The second asked whether the benefits of Lykos’ therapy along with a proposed risk evaluation and mitigation strategy (REMS) outweighed the risks of treatment. The committee voted 10-1 against.
Lykos is seeking FDA approval of the MDMA capsule along with psychological intervention, also known as MDMA-assisted therapy, for PTSD.
"We are disappointed in today's vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention," Lykos CEO Amy Emerson said in a Tuesday afternoon statement.
"We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved.”
Heading into the meeting, the FDA raised concerns about the ability to conduct a fair clinical trial for an MDMA treatment.
“Midomafetamine produces profound alterations in mood, sensation, suggestibility, and cognition. As a result, studies are nearly impossible to blind,” the FDA wrote in briefing documents that were posted ahead of the meeting.
The committee members all echoed the same thing as they explained their votes after the marathon nine-hour meeting: There just aren’t enough data to support MDMA’s entry to the market—yet. All agreed Lykos’ offering is promising.
“I absolutely agree that we need new and better treatments for PTSD, especially in the somatic treatment space. However, I also note that premature introduction of a treatment can actually stifle development and stifle implementation and lead to premature adoption of treatments that are either not completely known to be safe, not fully effective or not being used at their optimal efficacy,” said Paul Holtzheimer, M.D., deputy director for research at the National Center for PTSD, executive division. “I think this is a really exciting treatment. I'm really encouraged by the results to date, but I feel that both from an efficacy and a safety standpoint is still premature.”
Walter Dunn, M.D., Ph.D., who was the sole yes vote on question two, said he voted with an eye toward making a new treatment option available for patients with few options. But he had reservations.
“I wish we had a Likert scale in addition to our yes and no votes because yes, I voted yes, however low on my confidence about the risk-benefit,” Dunn explained.
He said the “greatest strength” of MDMA is also its “greatest liability,” and that’s the psychotherapy part of the treatment. Ultimately, that part isn’t under the purview of the FDA. Dunn also flagged that Lykos has not fully settled on the REMS strategy and so the committee did not get a chance to consider whether that helps tip the risk-benefit scale.
“It's probably 75% of the way there. You're definitely on the right track. I think a tweak here and there can address some of the safety concerns we brought up,” Dunn said.
But Dunn still cast a yes vote, which he explained: “I'm putting on my clinician hat … we are in dire need of new treatments for PTSD, and I'm especially sympathetic to the stories of our veterans that were here during the public commentary.”
As a former service member, Dunn understands that veterans need something to help with their PTSD, and MDMA could make a difference—with risks.
“As I like to tell all my trainees, there's no free lunch in medicine and what has the potential for benefit has the potential for harm,” he said. With the REMS issues resolved, Dunn thinks MDMA could go on to become a safe treatment in the right clinical context.
All of the committee members urged Lykos to keep going and researching. Consumer advocate Kim Witczak, executive director of advocacy group Woodymatters, commended the FDA and Lykos for bringing the application forward and asking the tough questions at the meeting.
“I don't think we're quite there yet,” Witczak said.
Lykos vowed to continue pushing to get MDMA approved. The FDA’s decision date for the application is Aug. 11.
This is the first time an FDA committee has ever reviewed a psychedelic treatment and it was the first time in 25 years that the FDA had even considered a new PTSD treatment.
The application for MDMA was supported by six phase 2 studies, two phase 3 trials and a long-term follow-up study. Both late-stage trials met their primary endpoint of improvement in PTSD symptoms compared to patients receiving placebo and psychological intervention.
Even if Lykos gets an FDA nod, the battle to get MDMA to patients is not yet over. The drug, commonly referred to as ecstasy, is still a Schedule 1 substance, along with heroin, marijuana and Quaalude. The drug would have to be rescheduled for use.