Compass Pathways' Psilocybin Drug Succeeds in Second Phase III Trial for Treatment-Resistant Depression

Compass Pathways reported that its synthetic psilocybin formulation COMP360 met the primary endpoint in the second of two pivotal phase III trials in treatment-resistant depression, clearing the path toward what would be the first regulatory filing of a classic psychedelic for a psychiatric indication. The company's shares surged more than 45% following the announcement.

In the COMP006 trial, two doses of COMP360 25 mg administered three weeks apart demonstrated a statistically significant reduction in depression severity compared to a 1 mg control, with a mean treatment difference of -3.8 points on the Montgomery-Åsberg Depression Rating Scale (MADRS), a clinician-rated measure of depression severity, at six weeks. The MADRS ranges from 0 to 60, and in antidepressant trials, differences of 2–3 points versus placebo are typically considered clinically meaningful.

The result closely mirrors the first trial, COMP005, which reported a -3.6-point advantage over placebo in June 2025. Together with earlier phase IIb data, COMP360 has now demonstrated efficacy in three consecutive controlled trials across 839 patients. Both phase III studies are continuing to 52 weeks.

The study also showed a favorable safety profile and rapid onset of treatment effect. Across both phase III trials, COMP360 was generally well-tolerated. Adverse events were mostly mild, occurred on dosing days, and the vast majority resolved within 24 hours.

In COMP006, the proportion of patients who achieved a clinically meaningful reduction in symptoms at six weeks was 39%. In COMP005, 25% of patients achieved a clinically meaningful reduction in symptoms at six weeks, and that improvement persisted through week 26 after just one or two doses. The 26-week data from COMP006 are expected in early Q3.

The CEO stated during a webcast on February 17 that the FDA has shown strong interest in an aggressive filing strategy, including the potential for a rolling submission and rolling review. The company plans to pursue a rolling regulatory submission with the FDA and aims to file a New Drug Application in the fourth quarter. The CEO indicated the company expects to be ready to launch commercially in the USA at the end of this year.

More than four million adults in the US are affected by treatment-resistant depression each year, and only Johnson & Johnson's Spravato (esketamine), a nasal spray approved for TRD in 2019 and subsequently approved also for major depressive disorder, has received FDA clearance for the condition. Spravato's annual revenue is nearing $2 billion.

The CEO noted that patients need 10 Spravato treatments by week 6 to achieve a similar effect to what is being seen with COMP360 at week 6, with one or two treatments. The CEO stated there are no approved drugs for depression, including Spravato, that offer rapid-onset, clinically-meaningful effect and durable outcomes from just one or two treatments.

The company acknowledged that it adjusted the COMP006 timeline in 2024, citing a high degree of scrutiny regarding unblinding, which is very relevant to the studies, meaning the possibility that patients or clinicians could infer treatment assignment because of the drug's noticeable effects, thereby undermining the integrity of a blinded trial.

The chief medical officer stated in a press release that across the very limited TRD treatment landscape, this potential treatment truly stands out for its extremely rapid and sustained efficacy, expressing gratitude to the participants, investigators, and clinical trial staff for their invaluable contributions to the trials.