Compass Pathways' Psilocybin COMP360 Meets Goal in Second Phase 3 Depression Trial

Compass Pathways said on February 17 that its psilocybin treatment COMP360 met the primary endpoint of COMP006, the second of its two Phase 3 trials in treatment-resistant depression, and that it aims to complete a New Drug Application in the fourth quarter, according to the company's release.

COMP360 is a synthetic, proprietary formulation of psilocybin. The results are company-reported data from Part A of a trial that is still running; 26-week data from Part B are expected early in the third quarter of 2026, Compass said.

A dose comparison, not a placebo

COMP006 is a randomized, double-blind study with 581 dosed participants in North America and Europe. It compares two fixed doses of COMP360, taken three weeks apart, at 25 mg (296 participants), 10 mg (142) and 1 mg (143). The primary endpoint was the difference between the 25 mg and 1 mg groups in change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) at Week 6.

The 25 mg group improved by 3.8 points more than the 1 mg group (95% CI -5.8 to -1.8; p<0.001), Compass said. It reported that 39% of participants in the 25 mg arm achieved what it defines as a clinically meaningful reduction in MADRS, of at least 25%, at Week 6, and that improvement in the 25 mg arm was statistically significant from the day after dosing at every measured timepoint through Week 6.

The first Phase 3 trial, COMP005, compared a single 25 mg dose with placebo in 258 dosed participants and reported a 3.6-point difference at Week 6 in June 2025. Compass said that in COMP005, participants with a clinically meaningful response at Week 6 kept that effect at least through Week 26 after one or two doses.

Safety and the FDA path

In the 25 mg arm of COMP006, most treatment-emergent adverse events occurred on dosing days and 83% resolved within a day; the most common were headache, nausea, anxiety and visual hallucination. There were six serious adverse events in six participants (2%). Across both trials, Compass said serious adverse events of suicidal ideation occurred in fewer than 1% of participants, and the one serious event of suicidal behavior occurred in the 1 mg arm of COMP006. The chair of the independent data safety monitoring board said there was no evidence of a clinically meaningful imbalance in suicidality between arms in either study.

"These data strengthen our conviction in the highly differentiated profile for COMP360 and given the urgent need for new treatments in TRD, we are advancing our discussions with the FDA, with the goal of submitting an NDA in Q4 and securing approval," chief executive Kabir Nath said, as quoted by Psychiatric Times.

Compass said it has asked the FDA for a meeting to discuss a rolling submission and review.