While a CRL is a rejection of the NDA in its current form, it’s not a total snubbing of MDMA-assisted therapy. The CRL, which is transmitted directly to the sponsor and is not made available to the public, discusses why a submission is not approvable and, relatedly, how a sponsor might work to address these deficits if it wishes to resubmit.
According to Lykos, which released a statement late on Friday, the agency has requested an additional Phase 3 study to further study the safety and efficacy of the intervention. That’s very bad news for the company.
Lykos shared that it plans to request a meeting with the agency to ask it to reconsider its decision, “and to further discuss the agency’s recommendations for a resubmission seeking regulatory approval for midomafetamine capsules.”
According to the company, the issues raised in the CRL echo those raised during the AdComm in June. In its statement, Lykos stressed “concerns around the structure and conduct of the Advisory Committee meeting, including the limited number of subject matter experts on the panel and the nature of the discussion.”
“The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in over two decades,” said Lykos CEO Amy Emerson.
Jennifer Mitchell, lead author on Lykos’ Phase 3 publications, said that the agency’s decision to request another Phase 3 study “is a major setback for the field.”
For now, it’s back to the drawing board for Lykos, which may need a fresh cash injection to meet the challenge. If FDA won’t budge on its additional Phase 3 requirement, it sets Lykos back several years and presents a task that borders on Sisyphean.
The very little available data on how appeals (‘Formal Dispute Resolution Requests’, in agency parlance) over CRLs fare doesn’t paint a rosy picture, with the vast majority being officially denied. However, even appeals which are ‘denied’ might lead to a more favourable path to approvable than that dictated by the agency’s original review, as Torrente and Kaur note. As such, Lykos and its supporters might hope to find an opening through the dispute resolution process.