FDA Denies the Lykos Therapeutics Application for MDMA-Assisted Therapy

The FDA has rejected Lykos Therapeutics’ New Drug Application (NDA) for MDMA-assisted therapy for PTSD. The agency issued a Complete Response Letter to Lykos, stating that the data submitted were insufficient for approval and requested an additional Phase 3 study which could require years of research and significant funding.

The FDA’s decision was not unexpected after an FDA Psychopharmacologic Drugs Advisory Committee (AdComm) overwhelmingly voted against approving MDMA-AT for PTSD in June, citing concerns about potential safety risks, study design, and research methods. These concerns were echoed in the Complete Response Letter (CRL), which is not publicly available, but was discussed by Lykos today in public comments.

In a statement, Lykos CEO Amy Emerson expressed great disappointment. She emphasized the impact of the decision on military veterans, first responders, victims of sexual and domestic abuse, and “countless others suffering from PTSD.” 

“The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in over two decades,” said Emerson.

The veterans community and their supporters in Congress have been at the forefront of advocating for the approval of MDMA-AT for PTSD. They stress the high rate of suicide among veterans suffering from PTSD and the absence of effective treatment. In a statement issued by veterans advocacy organizations Healing Breakthrough and Heroic Hearts, who have been calling on the FDA to approve MDMA-AT, the groups said they were deeply concerned about the denial of the Lykos NDA. Calling the decision the “epitome of bureaucratic red tape,” the groups said that it will result in continued deaths.

“MDMA-AT is the most effective treatment ever developed for PTSD, a condition at the core of the Veteran suicide crisis that claims over 17 lives each day,” the groups said. “The FDA’s decision is a missed opportunity to embrace groundbreaking science, save countless Veteran lives, and honor the sacrifices made by those who served our country. If this critical treatment remains inaccessible, we face losing an additional 6,000 Veterans to suicide this year alone—and every year thereafter.”

MDMA-AT Opponents and Advocates Reflect 

In a statement on the social media platform X, Neşe Devenot, a senior lecturer in the University Writing Program at Johns Hopkins Krieger School of Arts & Sciences, posted comments that reflected the views of Psymposia, an advocacy group critical of FDA approval of MDMA-AT. Devenot wrote, “We applaud the FDA’s decision to reject Lykos’ application for MDMA-assisted therapy. As patient advocates, we believe this is a critical time for thoughtful action, accountability, and the establishment of the highest standards in psychedelics safety, efficacy, & harm reduction.”

In Psymposia’s public statement posted by Devenot, the group asserted that they were acting on behalf of veterans and others with PTSD. It charged that “Lykos has a history of cover-ups, data manipulation, and egregious psychological, financial, and sexual exploitation of patients that should be exposed, not ignored. The people who counted on Lykos to conduct their trials responsibly deserved better. The FDA followed the science and did not cave to political pressure funded by Lykos’ donors and investors.” 

Together with New York Magazine, Psymposia published a series of podcasts in 2021 and 2022, including episodes which documented the sexual abuse of one patient during the MDMA-AT clinical trials. Psymposia has not provided support for additional allegations. 

Psymposia’s statement asserts their belief in the potential of MDMA and other psychedelics to address “a range of indications.” The group writes that their “goal is to ensure that patients, veterans, and other vulnerable demographics seeking help are not exploited and abandoned by pharmaceutical companies. This decision protects the future of the psychedelic field by avoiding a rush to market with preventable harms, as occurred in the opioid crisis.” 

Devenot and other people affiliated with Psymposia offered statements during the public comment portion of the June AdComm meeting that were critical of Lykos and its NDA. In a letter to President Joe Biden signed by 61 members of the House of Representatives from both parties, lawmakers noted that certain groups and individuals voiced criticism of the NDA during the regulatory review process. “It is our understanding that while these critics may be well-intentioned, their criticism is not necessarily reflective of the science, but rather their personal ideological beliefs and biases related to the medicalization of substances like MDMA,” wrote the lawmakers. 

“While all Americans are free to voice their views on this and other topics of public interest, scientific evidence should not be ignored in favor of those who have been on a mission to discredit this promising treatment at all costs – especially when that would come at the cost of our servicemembers and Veterans,” lawmakers wrote. “Thousands of Veterans suffering from PTSD continue to take their lives each year. Current treatments clearly are not working well enough, and our Veterans can no longer wait.” 

 A Blow To The Research Community

The rejection of the Lykos NDA for MDMA-AT is a major blow to the psychedelic research community. The MAPS nonprofit organization, and the spin-off for profit MAPS Public Benefit Corporation which became Lykos Therapeutics in January, have been pioneers in the field of research into psychedelic therapies for more than three decades. 

Despite the setback, Lykos says it plans to request a meeting with the FDA to reconsider the decision and “further discuss the agency’s recommendations for resubmission seeking regulatory approval for midomafetamine [MDMA] capsules.” While not a public document, the CRL details why it did not approve the Lykos NDA. According to the Lykos statement, the concerns raised in the letter echo the criticisms presented in June by the AdComm. 

In its statement, Lykos asserted that, “The Company and other stakeholders have expressed concerns around the structure and conduct of the Advisory Committee meeting, including the limited number of subject matter experts on the panel and the nature of the discussion, which at times veered beyond the scientific content in the briefing documents. FDA itself has acknowledged potential problems with the Advisory Committee process and has opened a public docket seeking comments on how it can be improved.”

Since the June AdComm meeting, Lykos has detailed how it was addressing the questions raised by advisors and recently released new measures for additional oversight if the NDA was approved. While MDMA-AT has hit a roadblock, proposed therapies with other psychedelic compounds such as psilocybin are still in late-stage trials. Compass Pathways and Usona Institute are leading the research into psilocybin-assisted treatments. The FDA decision on MDMA-AT will shift the focus to these organizations and impact investment in companies seeking to develop other therapies that use psychedelic compounds. 

“Developing the first-ever clinical trial design to assess the safety and efficacy of midomafetamine-assisted therapy with patients suffering from moderate to severe PTSD is an enormously complex undertaking,” said Jennifer Mitchell, Ph.D., Professor of Neurology and Psychiatry and Behavioral Sciences at UCSF who was the lead author on Lykos’s Phase 3 research reports. “Over the course of many years, the researchers, with the support of our sponsor, Lykos, developed and executed Phase 3 studies that we believe demonstrated the approvability of this treatment. We did so in consultation with the FDA and with an agreed Special Protocol Assessment in place. The FDA’s decision to request another Phase 3 study is a major setback for the field.” 

For now, Lykos faces a challenging path forward potentially requiring costly research if the FDA insists on an additional Phase 3 study. According to the company’s statement, “Lykos will work diligently in the coming months to address FDA’s concerns and to take advantage of agency processes to resolve scientific disagreements. Following the FDA meeting, Lykos expects to provide an update on next steps for the resubmission.”

In the meantime, the FDA decision raises questions about training and credentialing programs for therapists seeking to provide MDMA-AT through Lykos and affiliated organizations. It also highlights the continuing role of therapists who provide this therapy without FDA approval.

Despite the FDA decision, public discussions about MDMA-AT have successfully accomplished rare bipartisan collaboration during a divided and fractious election season. Rep. Jack Bergman (R-MI) led the 61 House members of both parties to draft a letter to President Joe Biden in support of MDMA-assisted therapy. Another bipartisan letter to FDA Commissioner Robert M. Califf supporting MDMA-AT was drafted by members of the Senate. In an interview with Lucid News this morning, Rep. Bergman highlighted the high rates of suicide among veterans and said members of Congress who support MDMA-AT are not going to stop advocating for new mental health therapies that are supported by scientific research. 

“We’re not gonna quit if the FDA says no,” said Bergman. “We’re not gonna quit because we know that it’s the right thing to move forward with new breakthrough therapies.”