The FDA questioned data around Lykos Therapeutics’ MDMA-based therapy for post-traumatic stress disorder on Friday, less than a week before its advisory committee meets to discuss what could be the first new PTSD treatment in decades.
Patients who took Lykos’ psychedelic alongside psychotherapy sessions in two Phase 3 trials saw statistically significant improvements over patients on placebo. But regulators worry bias may have impacted those results.
MDMA, also known as ecstasy, is associated with “profound alterations in mood, sensation, suggestibility, and cognition,” the FDA noted in its briefing documents. As a result, about 90% of patients on treatment correctly guessed their assignment, as did 75% of those assigned to placebo.
The FDA’s Psychopharmacologic Drugs Advisory Committee will vote Tuesday on whether the data prove the treatment can effectively treat PTSD, and whether the benefits outweigh its risks.
“Several factors make these data challenging to interpret and complicate the benefit-risk assessment for this application,” the FDA wrote in its briefing documents.
Lykos’ candidate would be the first MDMA-based therapy approved for PTSD, a mental health condition that affects more than 13 million adults in the US. While a slate of companies are looking to treat mental health conditions with modified psychedelics, practical challenges remain, such as effectively blinding trials.
Drug pricing watchdog ICER recently raised its own concerns around whether Lykos’ trials were effectively blinded. In its own briefing documents, Lykos said an independent group of mental health professionals who were blinded to the study design conducted efficacy assessments over video conferences to minimize bias.
The agency also cited several safety concerns, including increases in blood pressure and pulse, and potential for abuse. As MDMA is currently a Schedule I drug — a class that prohibits medical use and has a high abuse potential — the FDA noted that MDMA would need to be rescheduled to allow prescription use.
Lykos noted that MDMA is known to increase heart rate and blood pressure, and added that the risk would be described in the proposed label and patients would be recommended to screen for cardiovascular risk prior to starting treatment.
“Although this application presents a number of complex review issues, it does include two positive studies in which participants in the midomafetamine arm experienced statistically significant and clinically meaningful improvement in their PTSD symptoms, and that improvement appears to be durable for at least several months after the end of the acute treatment period despite no additional doses of midomafetamine,” the FDA said in its briefing documents.
The FDA recommended several Risk Evaluation and Mitigation Strategies, including that the drug only be dispensed in certain healthcare settings, that patients are monitored while on treatment, and that patients are enrolled in a registry.