The first Phase 3 clinical trial of psilocybin for treatment-resistant depression has met its primary endpoint, marking a significant milestone for psychedelic therapies. On February 17, Compass Pathways reported that its second pivotal trial, COMP006, met its primary endpoint, making COMP360 the first classic psychedelic to produce two positive Phase 3 results.
The multi-dose trial enrolled 581 participants across North America and Europe and tested two fixed 25 mg doses of synthetic psilocybin administered three weeks apart against 10 mg and 1 mg comparator arms. At Week 6, the 25 mg group showed a mean treatment difference of -3.8 points on the Montgomery-Åsberg Depression Rating Scale versus the 1 mg group (p<0.001). The company reported that 39% of participants on the high dose achieved what it defines as a clinically meaningful MADRS reduction of at least 25%—a lower bar than the standard 50% threshold typically used to define response in antidepressant trials.
The first Phase 3 trial, COMP005, reported in June 2025, tested a single 25 mg dose against placebo in 258 U.S. participants and produced a similar separation of -3.6 MADRS points (p<0.001). In that trial, 25% of participants in the active arm met the 25% response threshold at Week 6. Across more than 800 dosed participants in both Phase 3 trials, the company reported a generally favorable safety profile. Most adverse events—headache, nausea, and visual hallucinations—were mild to moderate and resolved within 24 hours. Serious adverse events involving suicidal ideation occurred at a rate below 1%.
Compass plans an NDA filing by year’s end and has requested a meeting with the FDA to discuss rolling submission and review. Longer-term durability data from COMP006, tracking outcomes through 26 weeks, is expected in early Q3 2026.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.drugdiscoverytrends.com/first-phase-3-psilocybin-data-clears-the-bar-for-treatment-resistant-depression-but-how-high-was-the-bar/