ICER raps conduct of Lykos’ psychedelic trial for PTSD

The Institute for Clinical and Economic Review (ICER) typically focuses on the cost-effectiveness of new therapies, but in an unusual move has sharply criticised the design and conduct of clinical trials of Lykos Therapeutics psychedelic therapy for post-traumatic stress disorder (PTSD).

The latest version of ICER’s evidence report (PDF) on Lykos’ MDMA-assisted psychotherapy for PTSD points to “functional unblinding in the clinical trials and additional concerns around trial design and conduct” that it claims means it cannot deliver an assessment of its benefits and harms.

In Lykos’ therapy, MDMA – a Schedule 1 controlled drug commonly known as ecstasy or molly – is administered in combination with psychological intervention in a controlled setting. The MDMA is administered in the form of midomafetamine capsules.

The new report comes at a pivotal time for Lykos and the wider psychedelic medicines sector. Lykos is just weeks away from an FDA advisory committee meeting that will be the first to consider a psychedelic-assisted therapy, as well as the first assessment of a new approach to treating PTSD in 25 years.

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.

Lykos carried out two phase 3 trials of the MDMA-AP therapy, MAPP1 and MAPP2, that have been published in the journal Nature Medicine. In its report, ICER maintains that it was “not able to assess the extent that bias influenced reporting of benefits or the frequency with which there may have been misreporting of harms,” so could not arrive at a cost-effectiveness decision.

“PTSD can be a severe condition affecting nearly all aspects of an individual’s life, [and] current therapeutic options are insufficient for many people,” said ICER’s chief medical officer, David Rind, in a statement.

“It will be incumbent on regulators with complete access to primary data to carefully evaluate whether MDMA-AP has been proven safe and effective,” he added.

In comments filed after ICER’s first draft of the report was published, Lykos said the health technology assessment (HTA) body had not included “meaningful input” from groups representing patients, caregivers, and providers who have perspectives to share on the needs of those living with PTSD.

The company also said it had sought and received feedback from the FDA throughout the development programme for MDMA-AP.

The US regulator is scheduled to complete a priority review of the therapy by 11th August, putting Lykos first in line to bring a therapy based on a psychedelic medicine through to approval.

For now, deliberations on the cost-effectiveness of the approach and the financial viability of the business model will have to wait, although ICER has scheduled a public meeting for 30th May to discuss its latest evidence report on MDMA-AP.

Photo by Cristian Palmer on Unsplash