COMP360 Psilocybin for Treatment-Resistant Depression Achieves Primary Endpoint in Phase 3 Trial

Compass Pathways today announced the successful achievement of the primary endpoint in the ongoing phase 3 COMP006 trial evaluating 2 fixed doses of COMP360—a synthetic, proprietary formulation of psilocybin for managing treatment-resistant depression (TRD). The primary endpoint was the difference in change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores between the 25 mg and 1 mg groups at week 6. Two fixed doses—administered 3 weeks apart—of COMP360 25 mg vs 1 mg demonstrated a highly statistically significant reduction in symptom severity (P<0.001) and a clinically meaningful difference of -3.8 points in change at the primary endpoint.¹

Notably, COMP360 is the first classic psychedelic to consistently achieve a highly statistically significant result and clinically meaningful effect, with a generally well-tolerated and safe profile.

COMP006 is the second of 2 phase 3 trials evaluating COMP360. Across both COMP005 and COMP006 to date, COMP360 has generally demonstrated a well-tolerated and safe profile, with all treatment-emergent adverse events being mild or moderate in severity, and most resolving within 24 hours. The data confirms a statistically significant rapid onset from the day following administration and maintained at all measured timepoints through week 6 in both clinical trials in the 25 mg arm. Data from the first trial, COMP005, suggest that participants who saw a clinically meaningful reduction in MADRS maintained durable treatment effect through at least week 26, after just 1 or 2 doses. Also worth noting, retreatment with a second dose was well-tolerated by participants with a consistent safety profile.

“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,” said Guy Goodwin, MD, the chief medical officer at Compass Pathways. “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 1 or 2 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.”

Compass Pathways has also submitted a request for a meeting with the US Food and Drug Administration (FDA) to discuss a rolling submission and review.

“Across 3 robust, well-designed, and well-executed clinical trials involving more than 1000 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,” said Kabir Nath, the chief executive officer at Compass Pathways. “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.”

Goodwin, the Psychiatric Times February 2026 Special Report Chair, said this of psychedelics: “Psychedelic drugs are poised to integrate into mainstream psychiatry, challenging traditional pharmacotherapies that require long-term daily tablet taking.”² Read the entire Special Report in our interactive issue here.

References

1. Compass Pathways successfully achieves primary endpoint in second phase 3 trial evaluating COMP360 psilocybin for treatment-resistant depression. News release. February 17, 2026. Accessed February 17, 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

2. Goodwin G. Psychedelics: powerful tools for burdensome disorders. Psychiatric Times. 2026;43(2):17.