Lykos Therapeutics revealed late Friday that the U.S. Food and Drug Administration (FDA) told the company that they couldn’t approve its application for the use of midomafetamine capsules (MDMA) – along with other psychological interventions – to treat PTSD patients. 
Instead, regulators “requested that Lykos conduct an additional Phase 3 trial to further study the safety and efficacy of [MDMA].”
Lykos announced in a press release that it planned to ask the agency to reconsider.
“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,” Lykos CEO Amy Emerson said in the release. “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.”
Research Questions Persist
Not surprisingly, the agency’s ruling echoed objections brought up in June by an advisory panel.
Objections included:
- For starters, as regulators have already pointed out, it’s not difficult for someone under the influence of a psychedelic to tell when they’re under the influence of a psychedelic.
- Second, most of the study participants admitted to having taken MDMA before, potentially coloring their perspective.
- Also, some study participants brought up claims of misconduct during the therapy portion of the trial.
- Finally, questions swirled about a lack of reporting on side effects.
“It seems like there are so many problems with the data,” committee member and VA Maryland Health Care psychologist Melissa Barone had told NPR. “Each one alone might be OK, but when you pile them up on top of each other…”
And the Institute for Clinical and Economic Review, an independent nonprofit that typically produces cost analysis reports, weighed in as well.
“Despite two randomized trials of MDMA-AP, functional unblinding in the trials and additional concerns around trial design and conduct led to ICER concluding that the publicly available evidence is insufficient to assess the balance of benefits and harms,” ICER Chief Medical Officer David Rind, MD, said in a press release.
Joseph Tucker, CEO and director at Enveric Biosciences, a biotech firm, suggested a pair of obstacles this study simply couldn’t overcome.
“The thematic challenges that came to light in the Lykos [trial] largely focused around two elements: expectation bias and the delivery of the psychological therapy,” Tucker argued. “These are difficult to separate from any therapy that induces hallucinations and/or requires psychotherapy in the treatment protocol but would likely be eliminated as concerns for the impending next generation of non-hallucinogenic neuroplastogens.”
Promising Results
Lykos officials had argued that its existing research – including two Phase 3 clinical trials (MAPP1 and MAPP2) – backed up its submission. These randomized, double-blind, placebo-controlled studies evaluated the efficacy and safety of MDMA-assisted therapy in participants with severe or moderate-to-severe PTSD. Both studies, the company insists, showed measurable reductions in PTSD symptoms and improvements in functional impairment.
“Evidence of efficacy for MDMA-AT includes 2 positive adequate and well-controlled Phase 3 studies,” the application read. “Treatment with MDMA-AT resulted in statistically significant and clinically meaningful improvements in PTSD symptom severity with additional statistically significant, supportive evidence of clinically meaningful improvement in functional impairment due to PTSD.”
What’s Next for MDMA?
While conventional wisdom expected the FDA to balk at approval this time around, many argue that it shouldn’t discourage continued research.
“Although Lykos … has faced significant obstacles, the rejection of their MDMA clinical trial data shouldn’t diminish the exciting potential of psychedelic drugs for treating PTSD, treatment-resistant depression, and opiate addiction,” Lindus Health Advisory Board Member Acacia Parks, MD, said. “It’s vital to distinguish between the flaws of a particular study and the overall therapeutic value of psychedelics. The issues with Lykos’ program do not indicate that MDMA is ineffective for PTSD, nor do they undermine the future of psychedelic therapies in psychiatry. The emphasis must be on rigorously proving therapeutic benefits, recognizing that setbacks like these highlight problems in study design rather than the efficacy of the drugs themselves.”
Others stressed the importance of safety, and how it must be a priority moving forward.
“I join many in the scientific community in advocating for a balance between innovative treatments and appropriate guardrails,” CO-founder and Chief Psychologist at Stella Center, Shauna Springer, PhD, said. “Any approval of MDMA should not be a ‘yes or no’ question but a question of how this innovation will be provided based on the principles of ‘responsible innovation.’ All safety concerns, including dosage, treatment settings, appropriate staffing, and the requirements for safe delivery protocols, need to be addressed before the FDA can approve this treatment.”
Further Reading
Why FDA Panel Rejected MDMA for PTSD Treatment
Nonprofit Not Ecstatic About MDMA’s Ability to Treat PTSD
The Long Road Toward Equitable MDMA Treatment in the United States
