Lykos' MDMA Therapy Nears Key Advisory Review

An FDA advisory committee is set to convene on Tuesday to evaluate the potential benefits of Lykos Therapeutics' psychedelic-assisted therapy for post-traumatic stress disorder (PTSD). This therapy, involving the use of MDMA (3,4-methylenedioxymethamphetamine), known commonly as ecstasy, marks the first PTSD therapeutic to undergo FDA assessment in the 21st century. The advisory committee's recommendation will be non-binding, with the FDA making its final decision on August 11 upon completing the New Drug Application evaluation.

MDMA was originally synthesized in 1912 but gained attention in psychiatric circles during the 1970s and 1980s. However, in 1985, it was classified as a Schedule I drug by the Drug Enforcement Administration, effectively halting most research. Interest was rekindled in the 1990s when the FDA approved clinical trials for its use in pain relief for terminal patients. Lykos Therapeutics, then known as MAPS Public Benefit Company, spearheaded significant research into MDMA's therapeutic potential.

Lykos recently completed a Phase III trial, demonstrating that about 70% of participants no longer met PTSD criteria post-treatment. Independent studies corroborated these findings, showing benefits lasting up to a year. Given this promising data, industry experts like Cybin CEO Doug Drysdale anticipate FDA approval.

The potential approval of MDMA-assisted therapy addresses a critical gap in PTSD treatment options, a sentiment echoed by multiple stakeholders. PTSD impacts roughly 7% of adults, with higher prevalence among veterans. The Veterans Administration is notably funding psychedelic studies across the U.S., including an upcoming MDMA study at the VA Palo Alto Health Care System/Stanford University, focusing on PTSD severity and quality of life improvements.

Standard PTSD treatments are limited, often involving selective serotonin reuptake inhibitors (SSRIs) which can take months to show effectiveness and come with side effects. The FDA briefing documents highlighted this unmet need, noting that current treatment response rates seldom exceed 60%, with full remission rates at 20% to 30%.

Approval of MDMA-assisted psychotherapy could provide a much-needed alternative. Currently, therapists without special licenses cannot legally dispense MDMA or conduct related research, as noted by Avigail Lev, founder and director of the Bay Area CBT Center. Approval would enable psychotherapists to explore new methods of treating trauma and related conditions like anxiety and depression.

Despite the significant promise, challenges remain. David Feifel, professor emeritus of psychiatry at the University of California, San Diego, cautions that MDMA's approval is not guaranteed. The Institute for Clinical and Economic Review (ICER) has expressed concerns about trial design and the potential bias from participants knowing their treatment status.

The FDA's briefing documents also noted "functional unblinding" issues in the trials, where participants and session monitors could guess the treatment assignments based on observed behaviors. Additionally, there were concerns that trial investigators might have underreported negative outcomes due to perceived pressure for the trial's success.

ICER's scrutiny of trial designs is routine, but its engagement with trial participants and public commentary is unusual, according to experts like Feifel. Lykos CEO Amy Emerson highlighted that their Phase III studies were designed with the FDA, using the Special Protocol Assessment process. Lykos also critiqued ICER for ignoring significant unmet medical needs and relying on limited stakeholder perspectives.

Looking forward, if MDMA is approved, the U.S. Drug Enforcement Administration would need to reschedule it from Schedule I within three months, with states following suit. This rescheduling could simplify research processes, making it easier to study other psychedelics with potential medical benefits.

Sam Clark, CEO of Terran Biosciences, which is also developing psychedelic therapies, noted that this regulatory change would significantly impact research in the field. Conducting research on a Schedule I drug currently requires a difficult-to-obtain license, slowing scientific progress. Rescheduling MDMA could thus pave the way for broader exploration of psychedelic compounds in medical contexts.