ICER Identifies 'Substantial Uncertainties' in Lykos' MDMA Trials Before Adcomm

Concerns over potential study bias have led the Institute for Clinical and Economic Review (ICER) to express reservations about accurately evaluating the net benefit of Lykos Therapeutics’ investigational MDMA-assisted therapy for post-traumatic stress disorder (PTSD). In a draft report released on Tuesday, ICER highlighted various issues that may have compromised the integrity of the clinical trials.

The watchdog group noted that investigators, therapists, and patients involved in the studies had strong pre-existing beliefs about MDMA’s effects, which could have influenced the reporting of both positive and negative outcomes. Many of the trial therapists and participants were drawn from communities already inclined to view psychedelics favorably, which ICER suggests could skew the results.

The draft report suggests that the enthusiasm for psychedelics in these communities resembles a quasi-religious fervor more than a scientific evaluation of pharmaceutical products. These strong beliefs were not only prevalent among community members but were also imparted to patients participating in the trials, potentially affecting their perceptions and reports of the treatment’s efficacy and safety.

ICER also pointed out that there were reports of pressure to present the trial results in a favorable light. Some participants and therapists recounted experiences of being encouraged to report only positive outcomes, while negative experiences were downplayed or omitted. In some cases, severe negative outcomes were allegedly reinterpreted as indicative of an appropriate treatment response, according to ICER. Furthermore, some patients were reportedly excluded from long-term follow-up studies, which ICER suspects was an attempt to keep negative outcomes from affecting the overall data set.

Another significant issue raised by ICER is that the trials were "essentially unblinded." The distinct psychoactive effects of MDMA made it easy for patients to discern whether they were receiving the active treatment or a placebo. Nearly all participants who received MDMA correctly identified their treatment, thereby potentially introducing bias.

In reaction to ICER’s findings, Lykos Therapeutics expressed disappointment in a public comment. The company argued that ICER's draft report overlooks the substantial unmet medical need for PTSD treatments and relies on a narrow range of stakeholder perspectives. Lykos contends that the assessment focuses on areas that fall under the FDA’s jurisdiction, particularly regarding the evaluation of a drug’s safety and efficacy.

This draft report comes at a critical time for Lykos, as the company is preparing for an FDA Psychopharmacologic Drugs Advisory Committee meeting scheduled for June 4, 2024. The panel, composed of external experts, will review Lykos’ application to use MDMA as a treatment for adults with PTSD in combination with psychotherapy and other mental health support measures. The outcome of this meeting will be pivotal for Lykos’ efforts to bring MDMA-assisted therapy to market.

The concerns raised by ICER underscore the complexities and challenges involved in evaluating novel treatments, particularly those involving substances like MDMA that come with a history of both therapeutic promise and regulatory scrutiny. The discussion around Lykos’ investigational therapy highlights the broader issues of study design, participant selection, and the potential for bias in clinical research, setting the stage for rigorous evaluation at the upcoming FDA advisory committee meeting.