COMP360 Psilocybin Sustains Depression Benefit Through 26 Weeks

Two fixed doses of COMP360, an investigational synthetic psilocybin formulation, produced a reduction in depressive symptoms that was maintained through 26 weeks in more than a third of participants with treatment-resistant depression (TRD).¹ The finding comes from newly reported 6-month data in Compass Pathways’ phase 3 COMP006 trial.¹

The results extend earlier week 6 findings and add longer-term evidence on durability of effect.² For a population that has cycled through multiple failed antidepressant trials, sustained benefit at 6 months would be clinically relevant if confirmed through peer review.³

“Against a high level of chronicity and treatment resistance, this achievement at scale is remarkable in one of psychiatry’s most underserved patient populations,” said Guy Goodwin, chief medical officer of Compass Pathways, in a statement. “For a condition that places profound burden on patients, families and the healthcare system, COMP360 has the potential to establish a new standard of care and fundamentally change what patients and clinicians can expect from treatment.”

COMP006 is a randomized, double-blind Phase 3 trial enrolling 581 participants with TRD across North America and Europe.⁴ Participants were assigned 2:1:1 to 2 administrations, 3 weeks apart, of COMP360 25 mg, 10 mg, or 1 mg, with the 1-mg dose functioning as an active comparator.²,⁴ The trial includes a blinded period through week 9 (Part A), a blinded extension through week 26 (Part B), and an open-label period through week 52 (Part C).⁴

The primary endpoint, change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 6, was met with a statistically significant difference favoring the 25-mg arm over the 1-mg arm.² In the newly reported Part B data, 39% of participants receiving 25 mg achieved a MADRS reduction of ≥ 25% by week 6, a response reported as maintained on average through week 26.¹ Nearly 30% of participants who had responded but not remitted by week 6 went on to achieve remission after the second dose.¹

Serious adverse events occurred in 6.3% of the 1-mg arm and 5.7% of the 25-mg arm through 26 weeks.¹ The most commonly reported adverse events were nausea, headache, anxiety, and visual hallucination, occurring predominantly on dosing days.1 Most treatment-emergent adverse events across both COMP005 and COMP006 have been described as mild to moderate and largely resolved within 24 hours.⁵

TRD, generally defined as inadequate response to ≥ 2 adequate antidepressant trials, affects an estimated 2.8 million of the 8.9 million US adults with medication-treated major depressive disorder.⁶ No single treatment has emerged as a dominant standard of care in patients who fail multiple trials.

COMP360 is a proprietary synthetic formulation of psilocybin, a 5-HT2A receptor agonist, administered with psychological support rather than taken as a daily oral medication.² The program received FDA Breakthrough Therapy designation for TRD in 2018.⁷ A companion trial, COMP005, evaluated a single 25-mg dose against placebo in 258 participants and previously met its primary endpoint at week 6.³ A rolling new drug application submission to the FDA is underway, with completion anticipated in the fourth quarter of 2026.¹

Compass Pathways executives have described the rapid onset of effect, detectable as early as the day after dosing, as a distinguishing feature relative to standard antidepressants.⁸ Detailed subgroup analyses, remission rates, and complete long-term safety tables remain pending new drug applicationication.²

Several limitations warrant attention before these findings inform practice. Functional unblinding, a recognized issue in psychedelic trials given the drug's perceptual effects, may influence blinded outcome assessments and has not been addressed in the disclosures to date.² COMP360 also remains a Schedule I controlled substance, and Drug Enforcement Administration rescheduling would be required before any US commercial launch following potential FDA approval.¹

“The COMP006 data further strengthens our robust clinical package for COMP360” said Kabir Nath, Chief Executive Officer of Compass Pathways, in a press release.¹ “We are convinced this profile will lead to a profound shift in mental health care—moving beyond daily or frequent administration towards an option potentially involving just a few treatments in a year that could be life changing for patients. As we advance launch preparations for TRD, we continue to have active interactions with the FDA with our rolling NDA submission underway and on track for final submission in Q4, and launch anticipated in the first half of 2027. We are excited by the data we have generated for COMP360 and thrilled for the millions of patients with TRD who could potentially benefit from our achievements.”

References

1. Compass Pathways. Compass Pathways announces six-month data from second Phase 3 trial confirming rapid and durable profile. News release. July 7, 2026. https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Announces-Six-Month-Data-from-Second-Phase-3-Trial-Confirming-Rapid-and-Durable-Profile/default.aspx

2. COMP360 psilocybin meets primary endpoint in second phase 3 trial for TRD. HCPLive. February 2026. https://www.hcplive.com/view/comp360-psilocybin-meets-primary-endpoint-second-phase-3-trial-trd

3. Compass Pathways' COMP360 psilocybin shows benefit in Phase 3 TRD trial. HCPLive. 2026. https://www.hcplive.com/view/compass-pathways-comp360-psilocybin-shows-benefit-in-phase-3-trd-trial

4. A study of COMP360 psilocybin therapy in treatment-resistant depression (COMP 006). ClinicalTrials.gov identifier: NCT05711940. Updated 2026. https://clinicaltrials.gov/study/NCT05711940

5. COMP360 safety data in Phase 3 TRD trials, with Steve Levine, MD. HCPLive. May 2026. https://www.hcplive.com/view/comp360-safety-data-phase-3-trd-trials-steve-levine-md

6. Zhdanava M, Pilon D, Ghelerter I, et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J Clin Psychiatry. 2021;82(2):20m13699. https://pubmed.ncbi.nlm.nih.gov/33989464/

7. COMPASS Pathways receives FDA Breakthrough Therapy designation for psilocybin therapy for treatment-resistant depression. Compass Pathways. Published on October 23, 2018. Accessed July 6, 2026. https://ir.compasspathways.com/News--Events-/news/news-details/2018/COMPASS-Pathways-receives-FDA-Breakthrough-Therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression/default.aspx

8. COMP360 psilocybin shows rapid, durable effect in TRD, with Steve Levine, MD. HCPLive. 2026. https://www.hcplive.com/view/comp360-psilocybin-shows-rapid-durable-effect-trd-steve-levine-md