Compass Pathways has reported that its second pivotal Phase 3 trial of COMP360 psilocybin in treatment-resistant depression (TRD) has met its primary endpoint, strengthening the case for regulatory submission in the US later this year.

The COMP006 study is the second late-stage trial evaluating COMP360, a synthetic formulation of psilocybin, in adults with TRD. The primary endpoint was the difference in change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between the 25 mg and 1 mg groups at Week 6.

According to the company, two fixed doses administered three weeks apart of COMP360 25 mg versus 1 mg demonstrated a highly statistically significant reduction in symptom severity, with a mean difference of -3.8 points at Week 6 (p<0.001). The result follows previously reported Phase 3 data from the COMP005 trial.

Kabir Nath, chief executive officer at Compass Pathways, said: “Across three robust, well-designed and well-executed clinical trials involving more than 1,000 participants, we have now demonstrated consistent, highly statistically significant results at the primary endpoint and a clinically meaningful effect. This is a remarkable achievement for the field of psychiatry – especially in the TRD population, where proving benefit has historically been extraordinarily challenging. 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.”

In COMP006, 39% of participants in the 25 mg arm achieved a clinically meaningful reduction in MADRS scores of at least 25% at Week 6. In COMP005, 25% of participants in the 25 mg arm reached that threshold at the same timepoint. The company also reported statistically significant rapid onset of effect from the day after administration, maintained through Week 6 in the 25 mg arm in both trials.

Durability data from COMP005 suggest that participants who achieved a clinically meaningful reduction at Week 6 maintained effect through at least Week 26 after one or two doses. For COMP006, Part B 26-week data are expected in early Q3 2026.

Guy Goodwin, chief medical officer at Compass Pathways, said: “TRD patients have extremely limited treatment options, and the unmet need remains profound. The promising clinical profile of COMP360 reinforces our belief in its potential to set a new standard of care for this population. These results redefine rapidity and durability for TRD patients with onset as early as the next day and, for those who respond, effects from just one or two doses lasted at least through 26 weeks, alongside a well-tolerated safety profile. Across the very limited TRD treatment landscape, this potential treatment truly stands out for its extremely rapid and sustained efficacy. We are incredibly grateful to the participants, investigators, and clinical trial staff for their invaluable contributions to our trials and for making this significant progress possible.”

Across both Phase 3 trials to date, COMP360 has shown what the company described as a generally well-tolerated and safe profile, with most treatment-emergent adverse events reported as mild or moderate. The majority occurred on the day of dosing and resolved within 24 hours. In COMP006, 6 participants (2%) in the 25 mg arm experienced treatment-emergent serious adverse events. Across both studies, the rate of serious adverse events related to suicidal ideation was reported as less than 1%, with one event of serious suicidal behaviour occurring in the 1 mg arm of COMP006.

The independent Data Safety Monitoring Board stated that there were no new, unexpected or concerning safety findings and no evidence of a clinically meaningful imbalance in suicidality between treatment arms.

Compass Pathways has requested a meeting with the U.S. Food and Drug Administration to discuss a rolling submission and review, and expects to complete a New Drug Application in Q4. If accepted, COMP360 would become the first classic psychedelic therapy to secure approval for TRD, marking a significant regulatory milestone for the field.