Lykos’ MDMA-Assisted Therapy Faces Landmark Adcomm
03 Jun 2024
Phase 3
Pictured: A prescription bottle over a groovy neuro background/ Nicole Bean for BioSpace
On Tuesday, an FDA advisory committee will meet to discuss the relative merits of Lykos Therapeutics’ psychedelic-assisted therapy for post-traumatic stress disorder—the first therapeutic for PTSD to undergo FDA scrutiny in this century.
The recommendation of the FDA’s Psychopharmacologic Drugs Advisory Committee is non-binding and will be considered by the FDA on August 11, when it completes its New Drug Application evaluation.
An approval of MDMA (3,4-methylenedioxymethamphetamine)— perhaps better known as ecstasy—to treat PTSD is expected to send major vibrations through the mental health community. The repercussions will affect not only treatment but research and are likely to spill over to other emerging psychedelic-assisted therapies.
“MDMA was developed in 1912 but didn’t really start to gain use in psychiatric practice until the 1970s and 1980s,” Sam Clark, CEO of Terran Biosciences, which is also developing psychedelic therapies, told BioSpace. “Then [in 1985] it was placed on a list of Schedule I drugs,” defined by the Drug Enforcement Administration as “drugs with no currently accepted medical use and the high potential for abuse.”
Research all but stopped until the 1990s when the FDA approved a clinical trial for pain relief in terminal patients. Lykos, then called MAPS Public Benefit Company, began investigating MDMA and “pushed it forward with a number of groundbreaking studies,” Clark said.
After completing Lykos’ Phase III trial, he said, “Around 70% of the patients no longer met the criteria for PTSD. That’s a big impact for patients!” Independent studies reported meaningful benefits and durations of up to 12 months.
“Given the data, I think [FDA approval] is highly likely,” Doug Drysdale, CEO of Cybin, another player in the psychedelics space, told BioSpace.
A High Unmet Need
The impact is so significant that the Veterans Administration is funding psychedelic studies throughout the U.S. for the first time since the 1960s. One of the first, studying an MDMA-assisted therapy, begins recruitment this year at the VA Palo Alto Health Care System/Stanford University. It measures changes in PTSD severity and in quality of life.
PTSD affects nearly 7% of adults during their lifetimes and is three to four times more common among veterans of recent wars. “We know the PTSD rates are higher among veterans who came back from Iraq and Afghanistan than in previous generations, and the last breakthrough in PTSD was decades ago,” Matt Saintsing, spokesperson for the Disabled American Veterans, told BioSpace.
“Veterans are looking for any new holistic treatments and are voting with their feet—leaving the country to get treatments they think may be safe and effective,” Saintsing said.
The broader availability of MDMA-assisted psychotherapy could fill a huge unmet need. “Patients with PTSD don’t have many options,” Clark noted. “They have standard therapy options, a few selective serotonin reuptake inhibitors (SSRIs), which take months to work and have side effects that include sexual dysfunction, and drugs that treat nightmares.”
In briefing documents released Friday, the FDA cited this unmet need, noting that response rates to current treatments “rarely exceed 60%” and less than 20% to 30% of patients achieve full remission.
Currently, without a special license, “Therapists can’t legally give MDMA to their clients [or] do their own research,” Avigail Lev, founder and director of the Bay Area CBT Center, told BioSpace.
Approval of Lykos’ therapy, she added, would “provide psychotherapists more flexibility to test new psychological methods, and would be a monumental step in treating and understanding trauma . . . as well as other symptoms such as anxiety, depression and grief.”
ICER’s Challenge
The great need for more effective PTSD treatment may figure into the advisory committee’s discussions, said David Feifel, professor emeritus of psychiatry at the University of California, San Diego and director of the Kadima Neuropsychiatry Institute. However, MDMA’s approval—though widely considered likely—is not a foregone conclusion.
The recently revised Evidence Report from the Institute for Clinical and Economic Review (ICER), which aims to assess the value of therapeutics and guide reimbursement, noted that the organization “heard from various people that feelings around psychedelics lead the community to engage . . . more like a religious movement than like pharmaceutical products.”
Not everyone engaged in the Lykos trials was a true believer, though. “Some entered the trial because there was finally something new to try,” David Rind, the chief medical officer at ICER, told BioSpace.
“Typically, in drug trials, it doesn’t matter how much [people] believe in the drug, because the trials are blinded,” Rind said. In those trials, participants don’t know whether they have the therapeutic or placebo. “In psychiatric clinical trials, blinding can be very difficult,” Rind continued. “In unblinded trials [belief in a therapeutic] gets heightened, so you have to worry about it more.”
The FDA also noted this “functional unblinding” in its briefing documents, saying that “the vast majority” of trial participants were able to accurately guess their treatment assignment. The FDA reviewers added, “it is likely that the in-session monitors could deduce a participant’s treatment assignment based on that participant’s behavior during the session.”
Perhaps more importantly, after speaking with participants, ICER reported there was pressure for the trial to succeed. The Evidence Report suggested trial investigators failed to accurately report negative outcomes.
Looking at trial design is normal for ICER, Rind said. “We always look at how a randomized trial was done, the comparators, and who the patients were.” That said, “It is unusual—but not the first time—for ICER to try to talk with participants in a trial.”
The psychedelics community doesn’t see it that way. “ICER usually doesn’t comment on a drug development program in this way,” Feifel told BioSpace. “It’s quite an anomaly.”
As Amy Emerson, CEO of Lykos, told BioSpace, “Our Phase III double-blind, placebo-controlled studies were designed with the FDA using the Special Protocol Assessment process.
“Usually, ICER works off publicly available information. We told them from the beginning it was a little early for the type of published report they work from,” Emerson said. Furthermore, she continued, “There was substantial input from 70 therapists between the draft and the final [report] that were not taken into consideration.”
In its response to ICER, Lykos wrote, “The ICER report 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.”
Underscoring that point, Drysdale added, “There should be no surprises for the FDA.”
Although advisory committee members probably are aware of the ICER report, “I think it will be largely disregarded, at least officially,” Feifel speculated.
In its briefing documents, the FDA also stated that “the assessment of safety presents numerous challenges,” citing the cardiac safety pro MDMA, “significant increases in both blood pressure and pulse,” and an incomplete QT assessment.
Opening the Door to Psychedelic Research
“If our MDMA capsules are approved by the FDA for use with psychological intervention, the U.S. Drug Enforcement Administration would be required to reschedule MDMA from Schedule I within three months of approval,” Emerson said. Then, individual states also will need to reschedule it according to their own processes.
“Rescheduling MDMA [to a lower risk category] will have a big impact for researchers in the space,” Clark hypothesized. Conducting research on a Schedule I drug requires a Schedule I license, which “is the hardest to get for research. It can take a long time, and the renewal process is difficult, which slows the pace of research dramatically.”
Rescheduling MDMA, therefore, “opens the door to reexamine other psychedelics that have medical value.”
Gail Dutton is a freelance science writer who has covered the biopharma industry since soon after its inception. She can be reached at gaildutton@gmail.com. Follow her on LinkedIn or see more of her work on MuckRack.
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