The Institute for Clinical and Economic Review has again flagged “substantial concerns” with Lykos Therapeutics’ data for its MDMA-based therapy for post-traumatic stress disorder and propensity for bias.
An independent drug pricing watchdog on Thursday concluded that there is not enough evidence to support Lykos Therapeutics’ MDMA-based treatment for post-traumatic stress disorder—and that the proposed regimen cannot be compared with other psychotherapies.
The Institute for Clinical and Economic Review (ICER) in a final report flagged “substantial concerns” with the “validity” of the data that Lykos used to support its drug application for an investigational MDMA-assisted psychotherapy (MDMA-AP) for patients with post-traumatic stress disorder (PTSD).
ICER pointed out that Lykos’ trials were “essentially, unblinded, with nearly all patients who received MDMA correctly identifying that they were in the MDMA arm of the trials.” The watchdog also cited multiple experts who said that those who were involved in the trials—participants, therapists and investigators—harbored “very strong beliefs” about the benefits of MDMA-AP, which further exacerbated the concerns of bias.
There were also instances of patients having been “encouraged” by study therapists to provide favorable reports of MDMA-AP while some therapists also “discouraged negative reports,” according to ICER.
The watchdog also found that there were not enough publicly available data to comprehensively assess the frequency of misreporting, participant beliefs and bias. This led the ICER to conclude that there is currently “insufficient” evidence backing MDMA-AP, and that the available data are also not enough to compare Lykos’ proposed regimen with other psychotherapies.
ICER’s final report on Thursday comes after Lykos suffered an overwhelming defeat in front of the FDA’s Psychopharmacologic Drugs Advisory Committee earlier this month. Voting 10-1, the panel of external experts agreed that even with a strict risk evaluation and mitigation strategy, MDMA-AP’s benefits do not outweigh its risks.
The advisory committee voted 9-2 that Lykos did not provide enough data to support the efficacy of its proposed regimen in PTSD. A consumer representative, who sat on the panel and voted against Lykos, also raised concerns about “selection bias, the functional unblinding” and the “potential for some misconduct and manipulating the trial results.”
ICER also held its own virtual public meeting to assess Lykos’ MDMA-AP. The majority of its panelists agreed that the biotech’s evidence was “not adequate” to illustrate a “net health benefit” for the proposed treatment regimen.
Centered on a popular psychedelic called 3,4-methylenedioxymethamphetamine, commonly known as ecstasy, Lykos’ MDMA-AP combines the psychoactive drug with psychotherapy and supportive mental health services for the treatment of PTSD.
The company’s drug application, which the FDA accepted in February 2024, is backed by data from several studies including the Phase III MAPP1 and MAPP2 trials. Late-stage evidence showed that MDMA-AP could significantly ease PTSD symptom burden in patients, while also providing significant functional improvements.
The FDA’s target decision date is set for Aug. 11, 2024.
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.
