Compass Pathways Advances in Second Phase 3 Trial for Psilocybin-Assisted TRD

LONDON – Compass Pathways PLC ADR, a UK-based mental health biotech company, announced that its second Phase 3 trial met the primary endpoint in evaluating COMP360, a synthetic formulation of psilocybin, for treatment-resistant depression (TRD).

The COMP006 study, which involved 581 participants across North America and Europe, tested two fixed 25 mg doses administered three weeks apart against a 1 mg control dose. At the six-week mark, the 25 mg group showed a mean difference of -3.8 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) compared with the control arm, with a p-value less than 0.001 and a 95% confidence interval of [-5.8, -1.8]. Thirty-nine percent of participants in the 25 mg arm achieved at least a 25% reduction in MADRS scores, which the company defined as clinically meaningful.

These results build on data from the first Phase 3 trial, COMP005, reported in 2025. That single-dose study in 258 U.S. participants produced a -3.6-point MADRS difference at week 6 (p<0.001) versus placebo, with 25% of the active group reaching the same 25% reduction threshold. Durability in COMP005 extended to week 26 for many responders, though longer-term outcomes in COMP006 remain pending and are slated for early Q3 2026 release.

Safety data from both trials indicated that treatment-emergent adverse events were mostly mild to moderate, typically resolving within 24 hours of dosing. Common effects included headache, nausea, anxiety, and transient visual changes. No new safety signals appeared.

Compass has requested a meeting with the U.S. Food and Drug Administration to discuss a potential rolling New Drug Application submission, with filing targeted for the fourth quarter of 2026. COMP360 holds Breakthrough Therapy designation from the FDA for TRD.

The news sent Compass Pathways shares sharply higher on February 17, rising more than 30% to close at $7.63 after opening around $7.83 and hitting an intraday high near $8.80, on volume exceeding 34 million shares.

The company described the combined Phase 3 program [encompassing over 1,000 participants across the two trials and prior Phase 2b work] as demonstrating rapid onset of effect, often from the day after dosing, and a profile that has proven difficult to achieve in TRD populations.

Independent observers note that while the endpoints were met with clear statistical significance, the absolute MADRS improvements of roughly 3.6 to 3.8 points remain modest relative to some benchmarks in antidepressant development. The 25% response threshold used by Compass differs from the more conventional 50% reduction often applied in the field, and full remission rates have not been detailed publicly for these studies. Questions about practical clinical implementation, including psychological support requirements and long-term durability, will likely factor into regulatory and payer discussions.

For the psychedelics sector, the dual positive readouts mark a concrete advance toward potential U.S. approval of a classic psychedelic therapy, following ketamine derivative Spravato. As more data emerge on sustained benefits and real-world application, Compass Pathways’ progress will continue to draw close attention from clinicians, regulators, and investors. Meanwhile, the path to regulatory review now appears clearer, though the ultimate place of COMP360 in treatment protocols will depend on fuller data and broader scrutiny.