Compass Pathways says a single dose of its synthetic psilocybin significantly reduced depression symptoms in patients who haven’t responded to standard treatments, marking a key milestone in what could become the first FDA-approved psychedelic therapy for treatment-resistant depression.
The company announced that its lead candidate, COMP360, met the primary endpoint in its Phase 3 COMP005 trial. Patients who received a 25 mg dose of the psilocybin compound saw a statistically and clinically significant reduction in symptom severity at six weeks compared to those given a placebo. The treatment produced a mean difference of -3.6 points on the Montgomery-Åsberg Depression Rating Scale (MADRS), a widely used tool for assessing depression levels.
COMP005 is the first-ever Phase 3 trial of a synthetic psilocybin therapy and the first late-stage study of any classic psychedelic to show a significant benefit over placebo. The trial enrolled 258 adults with treatment-resistant depression across 32 U.S. locations. Participants received a single dose of COMP360 or a placebo, alongside psychological support, and were tracked over multiple weeks.
Compass CEO Kabir Nath said the results reflect “scientific rigor” and bring the company closer to providing new options for patients who have not found relief from traditional antidepressants.
Safety data from COMP005, along with a second ongoing trial called COMP006, showed no new concerns. According to an independent data monitoring board, there was no meaningful imbalance in suicidality or other safety signals between the treatment and placebo arms.
The COMP360 program includes two large-scale trials. While COMP005 is studying the effects of a single dose, COMP006 is evaluating two fixed doses of psilocybin given three weeks apart. That second trial involves more than 500 participants across North America and Europe and is still underway. Compass says it plans to release 26-week follow-up data for COMP005 after COMP006 reaches a key milestone later this year.
COMP360 is a proprietary synthetic formulation of psilocybin, the hallucinogenic compound found in psychedelic mushrooms. Compass Pathways is developing the drug under the FDA’s Breakthrough Therapy designation, a status that could expedite its review.
The company said it intends to discuss the new COMP005 data with the FDA in preparation for potential regulatory filings.
“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, 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.”
