Lykos Therapeutics’ submission of midomafetamine (MDMA) capsules for the treatment of posttraumatic stress disorder was rejected Friday by the Food and Drug Administration (FDA), with officials requesting an additional phase 3 study, which will take several years to complete.
This was the FDA’s first decision involving a psychedelic drug used for a psychiatric indication. Lykos said it plans to request a meeting with the FDA to ask for reconsideration of its decision.
“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," Amy Emerson, Lykos Therapeutics’ CEO, said in a media release.
MDMA, also known as ecstasy, is an entactogen that is believed to increase an individual’s self-awareness and introspection. Lykos’ clinical trials included a novel psychotherapeutic intervention alongside MDMA sessions that Lykos said helps people access and process painful memories, so they can undergo therapy without becoming overwhelmed.
The concerns raised by the FDA in its rejection letter echo those of the agency’s independent Psychopharmacologic Drugs Advisory Committee, which in early June voted overwhelmingly against the approval of MDMA. Advisory committees’ recommendations are nonbinding, but the FDA typically follows them.
Among issues raised by the advisory committee were:
- Lack of evidence of durability of the treatment response.
- Allegations of sponsor/researcher bias and undue influence.
- Expectancy bias stemming from prior illicit use of MDMA by trial participants.
- Insufficient data on cardiovascular and hepatotoxicity risks.
- “Functional unblinding” arising from most researchers and participants correctly guessing who received the placebo versus active treatment.
- The role the psychotherapy played in the trial outcome, and the fact that psychotherapy is not regulated by the FDA.
The committee also focused on a documented case of serious sexual misconduct that occurred during a 2015 phase 2 trial. Notably, the journal Psychopharmacology on Saturday retracted three papers related to these phase 2 studies, noting that the study authors were aware of unethical conduct at one of the study sites but did not disclose that information to the journal or remove data generated by that site from their analysis.
Lykos took issue with what it called the limited number of subject matter experts on the advisory committee and that the discussion at times “veered beyond the scientific content” presented in the briefing documents. Lykos asserted that the FDA’s concerns “can be addressed with existing data, post-approval requirements, or through reference to the scientific literature.”
For more information, see the Psychiatric News article “Psychedelics’ Use as Medicine Hits Significant Roadblock.”
(Image: Getty Images/iStock/boonstudio)
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