Compass Pathways’ Phase 3 COMP006 trial showed COMP360 psilocybin delivered rapid, durable antidepressant effects in treatment‑resistant depression with a favorable safety profile, supporting the company’s rolling FDA NDA submission.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Compass Pathways has reported positive 26-week data from the ongoing Phase 3 COMP006 trial, further strengthening the clinical evidence for COMP360, its proprietary synthetic psilocybin formulation, in adults with treatment-resistant depression (TRD). The latest findings demonstrated rapid and sustained antidepressant effects for at least six months while maintaining a favorable safety profile, reinforcing results previously observed in the Phase 3 COMP005 study. The data support the company’s rolling New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA), with final submission expected in the fourth quarter of 2026.
Scientific and Clinical Context
Treatment-resistant depression remains one of psychiatry’s most difficult conditions to treat. Patients typically fail to respond adequately to at least two standard antidepressant therapies and often experience prolonged depressive episodes, recurrent illness, impaired quality of life, and an elevated risk of suicide. COMP360 is a synthetic, proprietary formulation of psilocybin under investigation as a novel therapeutic approach that differs from conventional daily antidepressants by offering the potential for durable clinical benefit after only a limited number of supervised treatment sessions.
Phase 3 COMP006 Results
The randomized, double-blind Phase 3 COMP006 study (NCT05711940) enrolled 581 patients across North America and Europe with highly chronic TRD. Participants had depressive episodes lasting more than three years on average and a history of more than six lifetime depressive episodes. The trial compared two fixed doses of 25 mg COMP360, administered three weeks apart, with 10 mg and 1 mg comparator doses over a 52-week treatment period.
The study had previously met its primary endpoint at Week 6. Newly reported Part B data showed that 39% of patients receiving the 25 mg regimen achieved a clinically meaningful reduction of at least 25% in Montgomery-Åsberg Depression Rating Scale (MADRS) scores by Week 6 and maintained that benefit through Week 26. Retreatment provided additional benefit, with nearly 30% of initial responders subsequently achieving remission during the blinded treatment period. Together with COMP005, the findings establish consistent evidence of rapid onset, durable efficacy, and reproducibility across two pivotal Phase 3 studies.
Safety Profile
COMP360 continued to demonstrate a generally well-tolerated safety profile, with no new safety signals identified during 26 weeks of follow-up. Most treatment-emergent adverse events were transient and occurred primarily on dosing days. The most frequently reported adverse events included nausea, headache, anxiety, and visual hallucinations. Serious adverse events remained uncommon and occurred at similar rates between treatment groups.
Clinical Implications
Chief Executive Officer Kabir Nath said the COMP006 results further strengthen the clinical package supporting COMP360 and reinforce confidence in the ongoing NDA submission. He noted that the therapy’s combination of rapid onset and durable benefit could shift depression treatment away from continuous daily medication toward a limited number of treatments each year for appropriate patients.
Chief Medical Officer Dr. Guy Goodwin added that demonstrating consistent efficacy across two large Phase 3 studies in a highly treatment-resistant population represents an important advance for psychiatric care. Independent clinical investigators also highlighted the potential value of a therapy capable of producing sustained symptom improvement in patients with longstanding, severe depression.
Regulatory Path Forward
Compass Pathways has initiated a rolling NDA submission with the FDA, with final submission expected in Q4 2026. If approved and following Drug Enforcement Administration (DEA) rescheduling, the company expects to launch COMP360 in the first half of 2027. Beyond TRD, Compass is also advancing a late-stage clinical program evaluating COMP360 for post-traumatic stress disorder (PTSD), further expanding its psychedelic-based psychiatry pipeline.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.