An FDA advisory committee on Tuesday overwhelmingly rejected Lykos Therapeutics’ investigational MDMA-assisted therapy for post-traumatic stress disorder due to safety concerns and how the company conducted its trials.
The FDA’s Psychopharmacologic Drugs Advisory Committee on Tuesday voted overwhelmingly against Lykos Therapeutics’ MDMA-assisted post-traumatic stress disorder therapy, citing issues with the biotech’s Phase III trials for its investigational treatment.
In a 10-1 vote, the panel of external experts agreed that the Lykos’ candidate does not outweigh its risk, even with a strict risk evaluation and mitigation strategy. The advisors also voted 9-2 on the matter of evidence, suggesting that Lykos had not provided sufficient data to show that the MDMA-assisted therapy was effective for post-traumatic stress disorder (PTSD).
“Based on selection bias, the functional unblinding, it just didn’t feel right,” Kim Witczak, consumer representative, said during the meeting, adding that the “potential for some misconduct and manipulating the trial results” also contributed to her vote against Lykos.
“This was a difficult decision for me. I think that some of the data [were] promising,” Elizabeth Joniak-Grant, patient representative and quality research consultant at the Injury Prevention Research Center of the University of North Carolina, Chapel Hill, said during the meeting.
“Given the 40% that had previously used MDMA, limited information about recruitment and recruitment coming through referrals, I really wonder how much that impacted the efficacy,” Joniak-Grant added.
The FDA will continue its review of Lykos’ investigational treatment with a target action date of August 11, 2024. The regulator is not required to follow the recommendation of the advisory committee, though it typically does.
Lykos is seeking approval to use MDMA—scientifically called 3,4-methylenedioxymethamphetamine but more commonly known as ecstasy—as oral tablets to treat PTSD, when combined with supportive mental health services like psychotherapy.
The biotech’s application is backed by two pivotal Phase III studies dubbed MAPP1 and MAPP2. According to the biotech’s briefing documents, posted ahead of the advisory committee meeting, the trials showed that the MDMA-assisted regimen “demonstrated clinically meaningful improvements in PTSD symptoms,” as evaluated by the Clinician-Administered PTSD Scale for DSM-5.
Last month, the Institute for Clinical and Economic Review (ICER) released a report pointing to flaws in the design of Lykos’ studies. ICER expressed concerns thatthe trials enrolled patients who had very strong prior beliefs regarding the use of MDMA, which could have skewed the recording of harms and benefits. The drug price watchdog also revealed that it had been made aware of pressures to report favorable results for Lykos’ candidate.
In its briefing document for Tuesday’s advisory committee meeting, the FDA also flagged important shortcomings in the studies’ design, noting that while the trials were designed to be double-blinded, “participants experienced functional unblinding due to the effects of the drug itself.”
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
