The US Food and Drug Administration (FDA) has rejected an application to allow the use of MDMA for the treatment of post-traumatic stress disorder (PTSD), bringing an end to several years of excitement about the prospect of the party drug becoming medicalized. After analyzing research submitted by drugmaker Lykos Therapeutics, the agency ruled that the data was too patchy, unreliable, and embroiled in scandal to be accepted.
Lykos’ application was based on a pair of Phase III clinical trials, one of which showed that 71 percent of PTSD patients who received MDMA-assisted psychotherapy no longer met the criteria for diagnosis four months after treatment. In a briefing document issued by the FDA in June, the agency acknowledged these findings, explaining that “participants appear to experience rapid, clinically meaningful, durable improvement in their PTSD symptoms.”
However, the document goes on to highlight numerous factors that detract from the reliability of this data. For instance, while the clinical trial was designed as a double-blind study – meaning neither patients nor therapists knew if a participant was assigned MDMA or a placebo – the drug’s very obvious effects make it impossible to hide the truth.
Known as “functional unblinding”, this led to around 90 percent of participants correctly guessing that they had been given MDMA. According to the FDA, “functional unblinding can introduce bias in clinical studies,” thus calling into question the validity of Lykos’ results.
The agency also complained that Lykos had failed to properly track the biological impact of MDMA, and that an assessment of the drug’s safety could therefore not be made. In particular, the compound’s cardiovascular effects may pose a risk to patients with high blood pressure or heart issues, and must therefore be rigorously studied before the drug can be approved for therapeutic use.
Other concerns about Lykos’ decision not to monitor MDMA’s potential for abuse – despite being directed to do so by the FDA – ultimately made up the agency’s mind. Voting 10-1 to reject the drug, an expert panel requested that Lykos conduct another Phase III trial, this time collecting all the necessary data.
Responding to the setback, Lykos CEO Amy Emerson said in a statement that “conducting another Phase III study would take several years,” but insisted that many of the FDA’s queries “can be addressed with existing data, post-approval requirements or through reference to the scientific literature.”
However, in an additional blow, three studies conducted by Lykos-affiliated researchers regarding the use of MDMA for PTSD have now been retracted by the journal Psychopharmacology. The journal’s editors decided to pull the studies in response to a sexual abuse scandal involving unlicensed Lykos therapists and a participant in a Phase II trial back in 2015.
Despite coming clean about the incident and banning those involved in 2019, the Multidisciplinary Association for Psychedelic Studies (MAPS) – of which Lykos is a subsidiary – didn’t disclose this vital information to the journal’s editors when submitting the papers, nor did it remove the data generated during the encounter.
Highlighting these ethical concerns at the FDA’s advisory committee meeting, researcher Nese Devenot from Johns Hopkins University claimed that “in addition to gross violations in Phase II, previously unreported violations include Lykos’s senior leadership having sexual encounters with a vulnerable individual who was then recruited into Phase III.”
“The most significant harms in Lykos’s clinical trials were not caused by MDMA but by the people who were entrusted to supervise its administration,” she said.
The FDA’s decision not to approve the drug means that Australia remains the only country in the world that allows the use of MDMA to treat PTSD. Lykos, however, says it will ask the FDA to reconsider, insisting that its data is robust and untainted by the transgressions of some of its therapists.
Source Link: FDA Snubs MDMA Following Flawed Trials And Sexual Abuse Scandal