FDA Panel Rejects MDMA for PTSD Application, But Recommendation Is Not Binding [FEATURE]

On Tuesday June 4, an independent advisory panel of the Food and Drug Administration (FDA) recommended that the agency not approve an MDMA-assisted therapy for the treatment of Post-Traumatic Stress Disorder (PTSD) application. The recommendation is only advisory -- not binding -- but the FDA ultimately agrees with advisory panel rejections of drugs two-thirds of the time.

The votes were not close. The Psychopharmacologic Drugs Advisory Committee (PDAC), on the basis of the research done so far, voted 10-1 that the proposed treatment's risks outweighed its benefits and 9-2 that it was not proven effective.

PDAC's review included results from two randomized, double-blind, placebo-controlled Phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA used in combination with psychological intervention, which includes psychotherapy (talk therapy) and other supportive services provided by a qualified healthcare provider, versus placebo with psychological intervention in participants diagnosed with severe or moderate to severe PTSD, respectively. Both MAPP1 and MAPP2 studies met their primary and secondary endpoints and were published in Nature Medicine.

The panelists' questions and comments betrayed concerns that while study participants were divided into two groups, one receiving the drug and one receiving a placebo, those who received the drug could tell they had the drug and not the placebo, due to the drug's psychoactivity. They also expressed concerns about possible bias among therapists who guided the sessions that could have influenced patient outcomes.

The hearing also put some of the tensions within the pro-psychedelics movement on display. For example, a member of the public who is wary of the intersection of psychedelics and big business, Ohio State University lecturer Brian Pace, described the entity spearheading the MDMA FDA effort, Lykos (formerly known as MAPS Public Benefit Corporation) as a "therapy cult," criticizing Multidisciplinary Association for Psychedelic Studies founder Rick Doblin for proselytizing for psychedelics.

Committee members also said that Lykos had not collected detailed data from participants on "positive effects" of the drug, which is commonly called "Ecstasy" because of its blissful effects.

"I absolutely agree that we need new and better treatments for PTSD," said Paul Holtzheimer, deputy director for research at the National Center for PTSD, as he voted that MDMA-assisted therapy's benefits did not outweigh its harms. "However, I also note that premature introduction of a treatment can actually stifle development, 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."

There has not been a new treatment for PTSD since the beginning of the century. The condition, first diagnosed about military veterans but now diagnosed more broadly, affects about 13 million Americans. It is linked to high suicide rates among veterans, and their suffering has prompted politicians and the public alike to revisit their attitude toward psychedelic therapies.

The session opened with remarks from Dr. Tiffany Farchione, director of the FDA's division of psychiatry, who noted that MDMA posed unique regulatory challenges, but also that the results of the Lykos studies were significant and enduring.

"Although the application presents a number of complex review issues, it does include two positive studies in which participants in the midomafetamine [MDMA] arm experienced statistically significant and clinically meaningful improvement in their PTSD symptoms," she said. "And that improvement appears to be durable for at least several months after the end of the acute treatment period."

Some 30 speakers addressed the panel before it voted and most supported moving forward. Typical was Cristina Pearse, who said she had developed PTSD after a childhood sexual assault, tried various psych medications, and even attempted suicide. MDMA-assisted therapy changed her life, she told the panel.

"What used to feel like a tsunami of overwhelming panic was now merely a puddle at my feet," said Pearse, who urged the FDA to approve the application. "How many more people need to die before we approve an effective therapy?" she asked. "As you weigh the risk, please keep in mind that this therapy can save many lives. I lost most of my life to this disease. I'm grateful to reclaim it now. But I wish this was an approved medication decades ago."

In the wake of the panel's decision, Lykos pronounced itself disappointed.

"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," Amy Emerson, Chief Executive Officer of Lykos Therapeutics said in a 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. We are grateful to the advocates, clinical trial participants and people living with PTSD who shared their testimony in the open public hearing and through written comments, and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD."

Reason for Hope, a nonprofit policy and advocacy organization dedicated to advancing safe and equitable access to psychedelic therapies to improve mental health and prevent deaths of despair, and the Veteran Mental Health Leadership Coalition, a member-based organization under Reason for Hope that focuses on increasing access to psychedelic therapies for Veterans, took the decision even harder.

"We are profoundly disappointed by the FDA Advisory Committee's vote against approval of MDMA for use with therapy (MDMA-AT) to treat post-traumatic stress disorder. Unfortunately, the Committee completely lost sight of the big picture amidst a novel and complex application," said cofounder of Reason for Hope and Founder & President of the Veteran Mental Health Leadership Coalition, Lieutenant General Martin R. Steele, US Marine Corps (Retired) in an email to supporters.

"It is hard to describe how tragic and heart-wrenching this vote was for so many of our veterans, who have been on the frontlines battling for more research and compassionate use access to this treatment. Indeed, we lose 17-44 veterans every single day to deaths of despair such as suicide or overdose -- often resulting from unresolved trauma in service to this country -- and the problem only seems to be getting worse. Despite rates of PTSD and suicide increasing for decades, we have seen little progress with new treatments, including no new FDA-approved drugs for PTSD in over 20 years."

Steele cited the "incredible success stories utilizing MDMA-AT" before blasting the panel, saying that "Yet, even despite the incredibly promising efficacy results in clinical trials developed in consultation with and agreed upon by the FDA, the Committee unfortunately could not seem to grasp the research nor post-approval regulation of a drug plus therapy combination. Members of the Committee seemed confused about what they were even voting on."

The PDAC's votes on Tuesday are a setback for MDMA-assisted therapy, but also just another step in a long, long process. The FDA will decide whether to accept the panel's recommendations in August, and the process will proceed from there, one way or another.