An FDA advisory committee voted against backing Lykos Therapeutics’ MDMA-based therapy for post-traumatic stress disorder, a blow to the biotech company’s efforts to bring the first ecstasy-based treatment to market in the US.
In advance of an Aug. 11 PDUFA deadline, the FDA’s Psychopharmacologic Drugs Advisory Committee voted 10-1 on Tuesday that the benefits of the treatment don’t outweigh its risks, even with a REMS program to more tightly control its use. The committee also voted 9-2 that the company’s data hadn’t proven that the product was effective in treating PTSD.
Lykos’s treatment is made up of midomafetamine capsules administered alongside psychotherapy sessions.
The FDA isn’t obliged to follow the committee’s recommendation, but it often does so. While studies of the treatment showed it improved patients’ PTSD, the FDA and the committee raised concerns about how the trial was conducted, saying that despite the placebo controls and blinding, the nature of the trial made it difficult for those to be effective in practice.
In briefing documents released prior to the meeting, the FDA said the Phase 3 studies were effectively unblinded due to “profound alterations in mood, sensation, suggestibility, and cognition” associated with MDMA. Some trial participants also had positive biases about the treatment going into the studies, according to an ICER draft report published last month.
“I think there has to be a more complex model and thinking outside the box of the regular, double-blind placebo-controlled trials, because I don’t think this is an adequately controlled trial by any means,” said committee chairperson Rajesh Narendran, psychiatrist at UPMC Western Psychiatric Hospital, who voted no.
Lykos tried to address the functional unblinding by getting “independent raters” who were blinded to study design and treatment to administer the Clinician-Administered PTSD Scale for DSM-5 assessment, CEO Amy Emerson told Endpoints News by email ahead of the meeting.
Other committee members accepted the functional unblinding, but said treatment safety was a major concern, especially the potential for MDMA abuse. In its presentation, the FDA said that Lykos didn’t collect adverse events related to abuse potential if they were deemed “positive, favorable or neutral,” such as patients having feelings of euphoria.
“I think there will be left and right diversion, illicit MDMA is going to soar, because it’s going to be all over the map” if the abuse liability is not properly characterized and addressed, Narendran said.
The FDA had recommended a REMS program to address the abuse risk. The risk program includes only dispensing the drug in certain healthcare settings, monitoring patients while they are taking the treatment and enrolling them on a registry.
PTSD affects more than 13 million adults in the US, and there have been no new treatments for the condition in more than 20 years.