AMBIGUOUS RESULTS

Compass's COMP360 holds depression benefit to 26 weeks after two doses

39% of patients on the 25 mg dose sustained a meaningful MADRS improvement from Week 6 through Week 26 in COMP006, as Compass moves toward a Q4 2026 NDA filing.

By AppliedXLJuly 7, 2026Trial NCT05711940

Executive Summary

Compass Pathways disclosed that its two-dose regimen of COMP360 sustained an antidepressant response from six weeks out to six months in a chronic, previously treatment-resistant population, extending a primary endpoint the trial had already met earlier in the year.
The disclosure leads with a subgroup responder rate rather than the trial's registered continuous endpoint, a framing shift that changes how the result should be read against the trial's own primary analysis.
This is the second of two pivotal Phase 3 trials feeding a rolling NDA submission that Compass expects to complete before year-end, with the durability data reinforcing the clinical package rather than establishing it.
COMP360 remains the only Phase 3 asset in treatment-resistant depression built on a 5-HT2A agonist, with the nearest mechanism peers in earlier-phase or adjacent-indication trials rather than head-to-head competition.

What was disclosed

Compass Pathways announced on July 7, 2026 that 26-week (Part B) data from COMP006, its second pivotal Phase 3 trial of COMP360 in treatment-resistant depression, showed 39% of participants on the 25 mg dose achieved a 25% or greater reduction in MADRS score by Week 6 and held that response through Week 26. Treatment-emergent adverse events were mostly transient and concentrated on the day of dosing, and serious adverse event rates were close across arms, at 6.3% for the 1 mg group and 5.7% for the 25 mg group. The trial enrolled 581 participants under NCT05711940, above its registered target of 572, in a population with depressive episodes lasting more than three years on average and more than six prior lifetime episodes. Compass+1

Probability of Success

Endpoint Met97%

Completes90%

Clinical Significance78%

Regulatory69%

How the endpoint was framed

COMP006's registered primary endpoint compares COMP360 25 mg against 1 mg on the continuous change from baseline in MADRS total score, not a binary responder threshold. That endpoint was already reported met in February 2026, with a mean treatment difference of 3.8 points and a p-value below 0.001. The July release instead foregrounds the share of patients crossing a 25% MADRS-reduction threshold at Week 6, sustained to Week 26, and attaches that framing to red flags for post-hoc emphasis, subgroup-only reporting, and an endpoint change, distinct from the trial's own registered comparison of continuous score change between the two doses. NCT05711940+1

The trial's design

COMP006 is a randomized, industry-sponsored Phase 3 trial testing two fixed doses of COMP360, taken three weeks apart, at 25 mg, 10 mg, and 1 mg against each other in adults with treatment-resistant depression defined as failure on two to four prior pharmacological treatments. The trial ran across twelve countries including the United States, United Kingdom, and several European sites, reached Active, not recruiting status in November 2025 once enrollment closed at 572, and carries a primary completion date of February 2026 that had shifted once, from March 2025, before enrollment finished. Part C continues as an open-label extension through Week 52. NCT05711940+1

The regulatory path

Compass said a rolling New Drug Application submission and initial FDA review are underway, with final submission on track for the fourth quarter of 2026 and a launch anticipated in the first half of 2027, contingent on FDA approval and DEA rescheduling of psilocybin. The company's first Phase 3 trial in this program, COMP005, previously reported rapid onset and durability through at least six months with a comparable safety profile, and the earlier Phase 2 COMP004 follow-up showed a longer time to relapse for the 25 mg dose than for 10 mg or 1 mg over 52 weeks. Compass+1

Where COMP360 sits

No other industry sponsor has advanced a 5-HT2A agonist to Phase 3 in treatment-resistant depression; the nearest mechanism peers, including lumateperone, DT120, LSD d-tartrate, and MM120, are running Phase 2 or Phase 3 trials in major depressive disorder or generalized anxiety disorder rather than the treatment-resistant population COMP006 targets. Field activity in 5-HT2A trials broadly has slowed, with 81 recent trials against 1,851 older ones. Against a population with a chronic disease course averaging more than three years per episode and no validated psychedelic-class approval in this specific indication, a durability signal that holds without erosion through Part C's Week 52 open-label extension would be the result that most clearly separates this program from a single-dose effect that fades. Compass

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