Following a poor showing for Lykos Therapeutics’ MDMA candidate for post-traumatic stress disorder at a recent FDA advisory committee meeting, the other shoe has dropped.
Friday, the FDA declined to approve Lykos’ midomafetamine (MDMA) therapy in patients with PTSD. Lykos had been seeking approval of its MDMA capsule along with psychological intervention, also known as MDMA-assisted therapy.
In its complete response letter to Lykos, the FDA said it could not approve the treatment based on data submitted to date, the company revealed in a release. In turn, the regulator has requested that Lykos run another phase 3 trial to further weigh the efficacy and safety of MDMA-assisted therapy for PTSD.
Lykos, meanwhile, said it plans to request a meeting with the FDA to ask the agency to reconsider its decision.
"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," Amy Emerson, Lykos’ CEO, said in a statement.
"While conducting another Phase 3 study would take several years, we still maintain that many of the requests that had been previously discussed with the FDA and raised at the Advisory Committee meeting can be addressed with existing data, post-approval requirements or through reference to the scientific literature,” she added.
The FDA’s rebuff comes a little more than two months after Lykos’ therapy failed to pass muster at a meeting of the agency’s Psychopharmacologic Drugs Advisory Committee (PDAC).
The panel of outside experts voted 9-2 against the treatment on the panel’s first voting question around whether the therapy is effective in patients with PTSD. On the second question around whether the benefits of Lykos’ treatment outweigh the risks, the committee voted 10-1 against the drug.
Ahead of the meeting, the FDA voiced concerns about the ability to conduct a fair clinical trial for an MDMA treatment, writing in briefing documents that “[m]idomafetamine produces profound alterations in mood, sensation, suggestibility, and cognition.”
In turn, studies on the drug are “nearly impossible to blind,” the regulator argued.
The committee members largely agreed with the FDA’s sentiments, though all agreed that Lykos’ candidate is promising.
Committee member Walter Dunn, M.D., Ph.D., who voted yes on the panel’s second question, said he supported the introduction of a new PTSD treatment but still had concerns. In addition to questions around the psychotherapy component of Lykos’ treatment, Dunn also flagged reservations on a proposed Risk Evaluations and Mitigation Strategy (REMS) and whether that could have tipped the risk-benefit scale.
Ultimately, Dunn said he figured Lykos’ MDMA therapy is “probably 75% of the way there," noting the company was “on the right track.”
“I think a tweak here and there can address some of the safety concerns we brought up,” Dunn said.
About a week after the advisory committee dust-up, Lykos sought to dispel some of the concerns raised about its therapy amid a rapidly growing conversation around the merits of MDMA-assisted treatment.
“We acknowledge that several issues raised during the PDAC meeting have now become the focus of public dialogue,” Emerson said in a letter to shareholders in mid-June.
She specifically addressed seven key concerns raised by the FDA committee, referencing questions on study blinding, bias from patients who previously used illicit MDMA, the use of therapy alongside the drug, the company’s REMS program and more.
In announcing the rejection Friday, Lykos noted that it had “concerns around the structure and conduct of the Advisory Committee meeting.” Specifically, the company called out the “limited” number of subject matter experts on the panel and the nature of the discussion itself, which “at times veered beyond the scientific content of the briefing documents.”
Elsewhere, the debate over MDMA-assisted therapy for PTSD has swelled far beyond the bounds of the biopharma world.
Earlier this month, 61 members of the U.S. House of Representatives and 19 senators released a pair of bipartisan letters pressing the White House and the FDA to approval Lykos’ proposed treatment.
The lawmakers noted that a staggering 13 million Americans suffer from PTSD, many of whom are veterans or survivors of sexual assault and domestic abuse. In turn, a suicide epidemic amongst veterans has emerged in the U.S., with more than 17 veterans dying each day.
The lawmakers pointed to the lack of innovation among approved PTSD drugs in the U.S., arguing that MDMA-assisted therapy comprises “one of the most promising and available options to provide reprieve for veterans’ endless PTSD cycle.
“The potential for groundbreaking advancements in PTSD treatment is within reach, and we owe it to our veterans and other affected populations to review these potentially transformative therapies based on robust clinical and scientific evidence,” the lawmakers wrote.