Chief among the public comments was a brief submission from Lykos Therapeutics itself (page 1).
“Lykos is disappointed by the ICER draft report as it discounts the significant unmet medical need for patients living with PTSD, relies on a limited number of stakeholder perspectives, and focuses on areas squarely within the FDA’s purview on the evaluation of safety and efficacy of drugs in the United States,” the letter states.
Much of the short letter then emphasises the significant unmet need for patients with PTSD, arguing that the report “neglected to include meaningful input from veterans, first responders, survivors of domestic violence and physical trauma”, and so on, who “have valuable perspectives to share on the needs of those living with PTSD.”
This substantive focus is largely because Lykos appears unwilling to enter discussion with ICER on its study design choices—both via the public comment process, but also throughout ICER’s research and drafting of the report, according to the nonprofit. Given its investigational therapy is under review by FDA, “the company will refrain from discussing details of the application in public comments on the ICER report”, Lykos wrote.
ICER pointed out that this is a common situation for a sponsor to find themselves in, given it regularly carries out reviews right ahead of FDA approval. “Nearly every review that ICER conducts involves therapies under review by FDA”, it said in its response to Lykos’ comments. “In the vast majority of those cases, companies find that they are able to engage with ICER and discuss reasons for specific design decisions.”
While keeping schtum on specific details regarding its study design and conduct, Lykos sought to emphasise its engagement with the FDA, which has included the agreement of a Special Protocol Assessment and a Breakthrough Therapy Designation, both in 2017.
“Given the novel nature of midomafetamine treatment, Lykos has consistently sought and received feedback from the FDA throughout the development program”, the letter signed by CEO Amy Emerson reads.
Perhaps most contentiously, however, Lykos claims that “the issues in the ICER report were not raised during the three meetings held between ICER and the Lykos management team prior to issuance of the draft report.”
ICER disagrees. “We want to emphasize that ICER did reach out to Lykos throughout the review”, it said in its response to Lykos’ letter. “Unfortunately, Lykos declined to collaborate with us,” the response continues, “and did not provide us with any relevant contacts to engage with (clinicians, patient advocates, researchers in the MAPP trials, etc.).”
This doesn’t chime well with a complaint made in a letter submitted by a group of around seventy therapists and trialists involved in Lykos’ Phase 3 studies (page 6), a version of which was originally published on Psychedelic Alpha (see Exclusive: Therapists and Trialists from Lykos’ Phase 3 MDMA-Assisted Therapy Studies Push Back on ICER’s Critical Draft Report).
“One hundred and nine therapists and principal/co-investigators contributed to the Phase 3 trials of MDMA-AP for PTSD”, the letter submitted as a public comment reads, continuing: “To our knowledge, none of them were consulted before the preliminary report was issued.”
Responding to the authors’ dismay at the lack of inclusion of investigators in the drafting of its evidence report, ICER again pointed to Lykos’ alleged lack of engagement in the process. “It is typically the case that investigators in manufacturer-sponsored trials will only engage in ICER reviews when the manufacturer gives permission and connects those investigators with ICER”, it said.
“Lykos was informed of the concerns ICER was hearing”, it continued, adding that it “would have been happy to engage with any investigators or therapists that Lykos had connected us with as a way to work through these concerns.”
In an apparent effort to further clarify its side of the story, ICER took issue with Lykos’ claim that “issues in the ICER report were not raised” in any of three meetings that took place between the two groups.
In its response, ICER explains that the first meeting was in August 2023, before the start of ICER’s review, when MAPS PBC said they felt the ICER review was early. ICER thus delayed the review by a month.
A second meeting took place in September 2023, and a third in March 2024, according to ICER. In that latter meeting, the nonprofit claims “the only engagement Lykos was willing to provide was to suggest that the price for MDMA used in a prior MAPS cost-effectiveness analysis should not be assumed as a placeholder price.”
According to ICER, Lykos “chose not to engage” over this time period.
In its reply to Lykos’ comment, ICER also reproduced an email it says it sent to the sponsor in early December 2023, notifying it of its line of inquiry into the Cover Story podcast and follow-up interviews with its producers, offering Lykos an opportunity to respond to the allegations. “As with other outreaches from ICER to Lykos, we received no substantive response.”
“Given this, it seems disingenuous to suggest that Lykos was unaware that ICER would be trying to evaluate concerns about the MAPP trials or that ICER did not try to provide Lykos an opportunity to engage”, ICER added.
On the topic of cost-effectiveness analysis, Lykos said in its comment that it was conducting its own that is “leveraging real-world cost estimates from a retrospective claims analysis along with data from its Phase 3 and long-term follow-up studies, the latter for which data will be published in the coming months.”