COMP360 Psilocybin for Treatment-Resistant Depression: Positive Phase 3 Efficacy Data

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Compass Pathways announced the successful achievement of the primary endpoint in the ongoing phase 3 COMP005 trial, the first of 2 phase 3 trials evaluating their synthetic, proprietary formulation of psilocybin for treatment-resistant depression (TRD), COMP360.¹

The randomized, double-blind, placebo-controlled study dosed 258 participants with TRD across 32 sites in the United States. Investigators aim to assess the efficacy and safety of a single dose of COMP360 25 mg vs placebo for reducing symptom severity in TRD. The primary endpoint was difference in change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores between the active treatment group and the placebo group at week 6. A single dose of COMP360 25 mg compared with placebo demonstrated a highly statistically significant reduction in symptom severity (P<0.001) and a clinically meaningful difference of -3.6 points (95% CI [-5.7, -1.5]) in change at the primary endpoint.

“The positive top-line results at week 6 from the COMP005 trial underscore the innovative potential of psilocybin treatment in mental health care for which Compass Pathways continues to pave the way,” said Kabir Nath, the chief executive officer of Compass Pathways. “We are proud of this significant progress, which reflects our scientific rigor, operational excellence and steadfast commitment to serving patients living with TRD. We eagerly anticipate further insights once we have the full dataset, and also look forward to findings from COMP006, which will explore the efficacy of 2 fixed doses. We remain focused on our goal of transforming the landscape of mental health treatment.”

The ongoing phase 3 COMP005 trial is the first study of an investigational, synthetic psilocybin, and the first study of a classic psychedelic to report phase 3 efficacy data. The second ongoing pivotal phase 3 COMP006 trial continues to enroll, with 26-week data expected in the second half of 2026. COMP006 is a randomized, double-blind study with 568 planned participants from North America and Europe. This study aims to compare the safety and efficacy of 2 fixed doses, taken 3 weeks apart, of 25 mg COMP360 to 10 mg COMP360 and 1 mg COMP360.

“As we continue our phase 3 program, we are very encouraged by the initial positive results and the highly statistically significant and clinically meaningful change in the MADRS score between the arms of the study 6 weeks after a single administration of COMP360,” said Guy Goodwin, MD, the chief medical officer of Compass Pathways. “This progress marks an important milestone for patients living with TRD and highlights the groundbreaking work Compass Pathways is doing to bring innovative treatments to those who have been failed by multiple currently approved available treatment options. This achievement provides hope that they can finally receive appropriate care and live the life they deserve. We are incredibly grateful to the participants, investigators and clinical sites for their invaluable contributions to this study.”

Additionally, according to the Independent Data Safety Monitoring Board, who reviewed safety data for COMP360, there were no unexpected safety findings and no clinically meaningful imbalance in suicidal ideation between treatment and placebo arms.

Compass Pathways plans to discuss these preliminary COMP005 data with the US Food and Drug Administration (FDA), which has not yet reviewed the data.

After the FDA rejection of Lykos Therapeutics’ midomafetamine (MDMA)-assisted psychotherapy tempered excitement for psychedelic therapeutics,² this positive data could generate new momentum.

References

1. Compass Pathways successfully achieves primary endpoint in first phase 3 trial evaluating COMP360 psilocybin for treatment-resistant depression. News release. June 23, 2025. https://www.businesswire.com/news/home/20250623615674/en/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression

2. Duerr HA. With MDMA on hold, what’s next for psychedelics? Psychiatric Times. September 11, 2025. https://www.psychiatrictimes.com/view/with-mdma-on-hold-whats-next-for-psychedelics