At a glance
- Investigational synthetic psilocybin therapy targeting treatment-resistant depression (TRD) across Phase 3 trials COMP005/COMP006.
- COMP006 trial shows -3.8-point MADRS reduction (25 mg vs 1 mg, p<0.001) at Week 6, confirming rapid, sustained TRD relief.
- Builds on COMP005’s -3.6-point win; 25-39% responders maintain effects ≥26 weeks after 1-2 doses.
- Mild/moderate TEAEs resolve in 24h; low SAEs (<1% suicidality), no new concerns per DSMB.
- FDA meeting requested for Q4 2026 NDA rolling submission, aiming to redefine TRD standards.
Written By: Pharmacally Medical News Desk
Compass Pathways plc has announced a major milestone with its COMP360 psilocybin therapy, successfully meeting the primary endpoint in the Phase 3 COMP006 trial for treatment-resistant depression (TRD). This builds on prior success in the COMP005 trial, positioning COMP360 as a potential game-changer in psychiatry for patients unresponsive to standard antidepressants. The results highlight rapid symptom relief and a favorable safety profile after just one or two doses.
Trial Details and Efficacy
The COMP006 trial (NCT05711940) evaluated two fixed doses of COMP360 25 mg versus 1 mg administered three weeks apart in 581 participants across North America and Europe.
The primary endpoint measured the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at Week 6, showing a highly statistically significant reduction in symptom severity (p<0.001) with a clinically meaningful mean difference of -3.8 points (95% CI: [-5.8, -1.8]).
In the 25 mg arm, 39% of participants achieved a clinically meaningful MADRS reduction (≥25%) at Week 6, with statistically significant rapid onset starting the day after dosing and sustained through all timepoints.
Complementing this, the COMP005 trial (NCT05624268) (258 participants) previously reported a -3.6-point difference (95% CI: [-5.7, -1.5]; p<0.001) versus placebo after a single 25 mg dose, with 25% of responders maintaining effects through 26 weeks. Over 40% of non-remitters by Week 6 in COMP005 remitted after a second dose, demonstrating durability without needing ongoing treatment.
Compass Pathways has not yet disclosed the precise molecular mechanism of COM360.
Safety and Tolerability
COMP360 showed a generally well-tolerated profile across both trials, with most treatment-emergent adverse events (TEAEs) mild or moderate and resolving within 24 hours 73% in COMP006 and 66% in COMP005 occurring on dosing days. Common TEAEs included headache, nausea, anxiety, and visual hallucinations. Serious adverse events (SAEs) were low: 2% (6 participants) in COMP006’s 25 mg arm and 5% (8 participants) in COMP005; suicidal ideation SAEs were under 1%, with one suicidal behavior case in COMP006’s 1 mg arm. The independent Data Safety Monitoring Board confirmed no new safety concerns or imbalances in suicidality.
Next Steps and Regulatory Path
Compass Pathways has requested an FDA meeting to discuss a rolling New Drug Application (NDA) submission targeted for Q4 2026, following consistent results across over 1,000 participants in three trials. COMP006 Part B 26-week data is expected in early Q3 2026.
CEO Kabir Nath emphasized the “remarkable achievement” in TRD, where efficacy has been historically challenging, reinforcing COMP360’s differentiated rapid and durable profile. Chief Medical Officer Dr. Guy Goodwin noted its potential to redefine standards, with effects starting the next day and lasting up to 26 weeks in responders, addressing profound unmet needs for the estimated 4 million U.S. TRD patients.
Dr. Guy Goodwin, CMO of Compass Pathways, highlights COMP360’s potential to transform TRD care amid limited options, with rapid onset the next day after one or two doses and effects lasting at least 26 weeks in responders, plus a well-tolerated profile. He praises its standout efficacy and thanks trial participants, investigators, and staff for enabling this progress.
TRD
Treatment-resistant depression affects those not responding to two or more antidepressants, worsening quality of life, comorbidities, and suicide risk compared to major depressive disorder. With depression projected as the top global disease burden by 2030 per WHO, innovations like COMP360 could transform care.
References
Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression, 17 February 2026, https://ir.compasspathways.com/News–Events-/news/news-details/2026/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-Second-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD, ClinicalTrials.gov ID NCT05711940, https://clinicaltrials.gov/study/NCT05711940
Efficacy, Safety, and Tolerability of COMP360 in Participants With TRD, ClinicalTrials.gov ID NCT05624268, https://clinicaltrials.gov/study/NCT05624268