FDA panel votes against Lykos’ pioneer psychedelic therapy

FDA independent advisors have comprehensively voted against the use of Lykos Therapeutics’ therapy for post-traumatic stress disorder (PTSD) based on MDMA, also known as ecstasy, in a setback for the nascent psychedelic therapy category.

Just two of the 11-member Psychopharmacologic Drugs Advisory Committee (PDAC) voted yes on the question of whether Lykos MDMA therapy midomafetamine – given in combination with psychotherapy – was effective in PTSD, with nine saying the data behind it was not strong enough.

On the issue of safety, the split was even worse for Lykos, with just one panellist concluding that the benefits of the therapy outweighed its risks in the context of a proposed risk evaluation and mitigation strategy (REMS) and 10 voting against. The therapy is the first new approach to treating PTSD in 25 years.

This is the first time that the PDAC has considered a psychedelic medicine – a sector which has attracted hundreds of millions of dollars in investment over the last few years – so the outcome of the meeting was under close scrutiny. The FDA isn’t bound to follow the PDAC’s advice, but the resounding verdict from the panel suggests Lykos is heading for disappointment when the regulator makes its final decision by 11th August.

Lykos chief executive Amy Emerson said the PDAC faced “a challenging and atypical assignment”, as it was evaluating a combined drug therapy and psychological intervention for the first time. Worryingly for the sector, though, quite a few other psychedelic therapies in development rely on psychotherapy-assisted drug treatment.

Emerson added the company would work with the FDA “to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system.”

The outcome of the meeting didn’t come out of the blue, as questions have been raised about the design and conduct of the two main clinical trials (MAPP1 and MAPP2) supporting Lykos’ application.

A report published by the influential Institute for Clinical and Economic Review (ICER) organisation last month concluded that it was not possible to exclude potential bias in the reporting of the treatment’s benefits and misreporting of its harms. Meanwhile, the FDA briefing document (PDF) released ahead of the meeting noted that “several factors make these data challenging to interpret and complicate the benefit-risk assessment.”

It has been well signposted that one of the main issues for developers and regulators is the difficulty in designing psychedelic studies with a blinded control group, given their obvious and overt effects on the brain.

Members of the PDAC voiced numerous concerns with the dataset, including the potential for bias due to “functional unblinding” of the study, problems with data collection, uncertainties about the efficacy of the therapy in the longer term, and the risk of side effects including cardiovascular and blood pressure problems and injury due to patient impairment, as well as abuse.

While the desperate need for new therapies for PTSD was acknowledged, panellist Paul Holtzheimer – who is deputy director for research at the National Centre for PTSD – warned that “premature introduction” of a treatment without robust evidence of efficacy and safety could stifle R&D into new approaches.

Photo by Christina Victoria Craft on Unsplash