Compass Pathways announced Monday that its psilocybin-based therapy achieved the primary endpoint in an early Phase 3 readout from the largest-ever study of the psychedelic compound for treatment-resistant depression. However, the company's stock price plummeted 36% before markets opened, suggesting investor disappointment with the magnitude of the therapeutic effect.
Trial Results and Safety Profile
A single dose of COMP360, Compass's psilocybin formulation, demonstrated a mean reduction of 3.6 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo in the randomized trial. The study, designated COMP005, tested a 25mg dose against placebo and represents one of two pivotal studies for the drug candidate.
Importantly, an independent data and safety monitoring board found no "clinically meaningful imbalance" in suicidal ideation between the treatment and placebo arms. This finding addresses a significant safety concern that emerged from an earlier Phase 2b study, which showed indications of increased suicidal ideation in the treatment arm compared to placebo, though not at a statistically significant level.
"We're pretty excited by ticking one of the big boxes we had to tick on the way to approval," said Guy Goodwin, Compass's chief medical officer. The FDA required that at least one trial compare psilocybin to inert placebo, despite the challenge of functional unblinding that occurs when patients can typically distinguish between receiving a psychedelic or placebo.
Comprehensive Clinical Program
The COMP005 trial is part of what Compass describes as the "largest randomized, controlled, double-blind psilocybin treatment clinical program ever conducted." The company has enrolled more than 900 patients across two pivotal studies, with the second trial, COMP006, testing the therapy across three different dose arms with results expected next year.
The multi-dosing approach in COMP006 helps address the unique challenge of blinding patients to psychedelic therapy. According to CEO Kabir Nath, patients in the trials are "overwhelmingly naïve to psychedelics," meaning they generally cannot determine their dose despite experiencing psychedelic effects during treatment.
"Some have a modest experience, some have a full-on experience, some have a profound experience," Nath explained. "But because they have no prior experience with psychedelics, it's hard for them to guess which dose they're on."
Market Context and Regulatory Landscape
The psychedelics sector has faced significant challenges following the FDA's rejection of Lykos Therapeutics' MDMA-based PTSD treatment in August. The regulatory setback, which cited problems including ethical issues and concerns over "functional unblinding," led to a 75% staff reduction at Lykos and contributed to declining market valuations across the psychedelics space.
"Positive data would be a big relief to the whole sector," Nath said, acknowledging the broader implications of Compass's trial results for the psychedelics industry.
The company has maintained strong regulatory engagement, holding breakthrough designation from the FDA and conducting discussions over six years. "They are very interested in psychedelics, but equally, there can't be any shortcuts, and they expect a robust clinical program," Nath noted.
Commercial Preparation and Market Opportunity
Compass raised $150 million in January and has sufficient cash to operate through its 2026 readout for COMP006. The company believes results from both pivotal trials will be necessary for FDA approval.
The treatment landscape for psychedelic therapies is being shaped by Johnson & Johnson's esketamine depression treatment Spravato, which launched in 2019 and has become one of the company's fastest-growing drugs. Spravato's success in building a network of treatment sites capable of administering psychedelic therapies under clinical supervision provides a foundation for Compass's potential launch.
"There are a lot of treatment sites that have their heads wrapped around what a psychedelic drug requires... so there is a much more fertile environment to launch into," Nath said.
The company has also engaged with payers to ensure coverage for administration and service fees associated with COMP360 for its estimated treatment population of 100 million patients.
Future Development Pipeline
Beyond depression, COMP360 is advancing through mid-stage trials for PTSD and anorexia nervosa, potentially expanding the therapeutic applications of psilocybin-based treatment. The current trial results could establish regulatory precedent for other psychedelics in development.
"This is the first data from a phase 3 [psilocybin] drug and that's exciting," Nath said, while acknowledging the inherent uncertainties in psychiatric drug development. "We remain confident. We believe this drug works for a significant amount of people. But this is a phase 3 trial in psychiatry, so you always have to temper that feeling."
