The FDA has rejected Lykos’ MDMA-assisted treatment for patients with post-traumatic stress disorder, a major setback for the company that had hoped to translate more than two decades of research into the first approved psychedelic medicine.
The FDA has requested that Lykos run an additional phase 3 study, according to the company’s late Friday announcement.
Lykos CEO Amy Emerson said in a statement that the request for an additional study was “deeply disappointing.” The company plans to ask the FDA to reconsider its request and says it will work “dilligently in the coming months” to address the agency’s concerns.
The decision was largely expected after an FDA advisory committee in June resoundingly voted against recommending the drug, raising extensive questions about how the company’s trial was run and the reliability of the data. Most of the advisers also voted that Lykos had failed to prove that MDMA was effective at treating PTSD. Lykos says that the issues raised in the FDA’s complete response letter mirrored those from the advisory meeting.
Emerson had expressed hopes that it could at least be asked for more data, and the chance at an approval.
With a rejection in hand, Lykos and MDMA’s future are up in the air. Emerson suggested that needing a new trial would be more difficult and harder to afford. The biotech raised $100 million in January, but that was mostly to advance the company through its regulatory filings and rescheduling work, had it been approved.
In the months ahead of the decision, both outside advisers to the FDA and the Institute for Clinical and Economic Review voiced concerns on the integrity of the clinical program. Reviewers specifically scrutinized the number of patients that were able to correctly guess that they were given the psychedelic and the failure on the part of Lykos to track positive adverse events. Feelings like euphoria could be associated with a risk of abuse — but were not tracked in the pivotal trials.
Larger ethical questions have also arisen, with reviewers at ICER citing unnamed trial participants who felt like they were pressured to report improvements in the trial. The primary endpoint of both Phase 3 programs was improvement in PTSD symptoms measured by a rating scale.
Lykos CEO Amy Emerson rejected claims that the results were tainted by bias and stood by the conduct of its trial investigators.
“I stand behind the rigor of the clinical trial and the way our data was collected,” she said in a recent interview with Endpoints. Emerson also backed the team overseeing the program, saying that everyone’s commitment was underpinned by the data’s promise.
“It wasn’t a group of all, like, psychedelic enthusiasts,” she said. “It was a group of people that are researchers.”
Anticipation of the decision reached a fever pitch on Capitol Hill when a bipartisan group of more than 60 representatives appealed directly to President Joe Biden in an early August letter, advocating on behalf of service members and veterans who may suffer from PTSD.
“If the data and evidence show that MDMA-AT is safe and effective at relieving the suffering that many Veterans face, then we owe it to them and the millions of others who are living with PTSD to make this treatment option available to them,” they wrote.
Another 19 senators said similarly in an Aug. 6 letter to FDA Commissioner Robert Calif, calling MDMA-assisted treatment a “promising therapy” and saying that America owes its veterans a new potential remedy.
That lawmakers from both parties felt compelled to lobby on behalf of a single FDA application exemplified both the dearth of treatments and the negative groundswell leading up to the agency’s choice.
Easing concerns
The company tried to assuage critics by announcing a three-pronged commercial strategy ahead of the FDA’s decision. It brought on a panel of advisors to consult with on the drug’s commercial rollout, prioritized well-known institutional behavioral health systems to administer the treatment, and said it would collaborate with other stakeholders on therapist training.
One center Lykos said it would’ve leaned on, had it received approval, is Sunstone Therapies, a Maryland-based facility that has been running an open-label, open expanded access program for Lykos that includes 46 patients. It did not participate in any of Lykos’ pivotal trials.
Sunstone CEO Manish Agrawal told Endpoints in an interview that Sunstone is “really focused on what safe and effective psychedelic assisted therapy looks like, irrespective of the drug.”
Lykos and its treatment — named midomafetamine — were born out of the work of the Multidisciplinary Association for Psychedelic Studies, or MAPS, a nonprofit launched by psychedelic scholar Rick Doblin. The work aimed to counteract stigma against MDMA after the DEA classified it as a schedule I drug in the 1980s. That listing is reserved for drugs that the agency considers to have no medicinal benefit and a high risk of abuse, such as heroin.
MAPS launched in 1986 to continue advancing studies using MDMA, and the focus on PTSD took hold in the early 2000s. Emerson began as a volunteer clinical program manager in 2003 while working at Chiron before ultimately becoming MAPS’ director of clinical research in 2012. Two years later, MAPS spun the PTSD work into a public benefit corporation, which rebranded to Lykos in January of this year.