Compass Pathways reports 52-week Phase 3 COMP005 results for COMP360 in treatment-resistant depression, with sustained MADRS reductions and no new safety signals.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Compass Pathways reported 52-week results from the Phase 3 COMP005 trial of COMP360, its synthetic proprietary formulation of psilocybin, in treatment-resistant depression (TRD). The open-label data showed sustained reductions in depressive symptoms following additional dosing, while participants who received their first 25 mg dose after placebo also showed meaningful reductions in depression severity.
Phase 3 COMP005 Trial Design
COMP005 was a randomized, double-blind, placebo-controlled Phase 3 study that enrolled 258 participants in the U.S. to evaluate the safety and efficacy of a single 25 mg dose of COMP360 versus placebo for reducing TRD symptom severity.
The trial comprised three sequential periods. Part A remained blinded through Week 6, with participants randomized 2:1 to a single 25 mg COMP360 dose or placebo. Part B remained blinded through Week 26 and allowed eligible participants to receive an additional dose matching their original treatment assignment. Part C was an open-label period from Week 26 through Week 52, during which eligible participants from either treatment group could receive a 25 mg COMP360 dose.
Approximately 70% of participants continued beyond Week 26 and entered Part C. About 80% of those entering from the original 25 mg group received another open-label dose, while approximately 90% of participants originally assigned to placebo received their first 25 mg dose in Part C.
Sustained Reduction in Depression Symptoms
Among participants originally randomized to 25 mg who received an additional dose in Part C, the mean reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score reached 13 points from baseline at Week 52. The reduction extended through the one-year follow-up, supporting the potential for additional dosing to deepen and prolong clinical benefit.
Participants originally assigned to placebo who received their first 25 mg COMP360 dose in Part C showed an average 10-point reduction in MADRS from baseline by the end of Part C. The finding provides additional evidence of a response following a single 25 mg dose, although its interpretation is limited by the open-label study design.
Across all participants who received 25 mg in Part C, including those receiving their first, second or third dose, response rates ranged from 40% to 45% between Day 1 and Week 6. Approximately 30% achieved remission during the same period. Response was defined as a ≥50% reduction in total MADRS score, while remission required a MADRS total score of ≤12 with no individual item scoring ≥4.
Interpreting the 52-Week Data
The one-year findings should be interpreted differently from results generated during the randomized, blinded portions of COMP005. Part C was an open-label, non-randomized continuation, and only participants who remained in the study beyond Week 26 entered this phase. As a result, attrition and selection effects may influence the long-term efficacy estimates, and participants who discontinued earlier were not represented in the Week 52 analysis.
Part C also lacked a concurrent placebo or active-control group. Therefore, changes in depressive symptoms during the open-label period cannot be attributed solely to COMP360 because natural symptom fluctuations, expectation effects and other aspects of ongoing clinical care may also contribute.
COMP360 is being developed within a structured clinical treatment model that incorporates psychological support rather than as a standalone pharmacological intervention. The reported clinical outcomes should therefore be considered in the context of the overall treatment protocol.
Safety and Regulatory Outlook
The safety profile in Part C remained consistent with Parts A and B. Compass reported that COMP360 was generally well tolerated, with no new safety findings.
The broader COMP360 Phase 3 program includes COMP006, an ongoing randomized, double-blind study with 581 dosed participants across North America and Europe. The trial is comparing two 25 mg doses given three weeks apart with 10 mg and 1 mg doses and includes follow-up through 52 weeks.
Compass Pathways said its rolling New Drug Application (NDA) submission and review are underway, with the final submission expected in the fourth quarter of 2026. The company expects a potential commercial launch in the first half of 2027, subject to FDA approval.
The COMP005 data add one-year follow-up to the evidence supporting intermittent COMP360 dosing in TRD. The durability signal is notable, but the open-label design and participant attrition mean the long-term findings require more cautious interpretation than the randomized portion of the trial.
Reference
Compass Pathways’ New 52-Week Topline Open-Label Data from Phase 3 COMP005 Trial Demonstrates Additional Benefit from Another COMP360 Dose in Part C Extending Durability Out to 1 Year, Compass Pathways, 09 September 2026
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.