Compass Pathways' COMP360 becomes first classic psychedelic to prove durable six-month benefit in TRD

Compass Pathways plc (Nasdaq: CMPS) [has reported ](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)26-week data from its second Phase III trial of [COMP360](https://app.allsci.com/drugs/ASC-DR-0000000026182-1.0-1772718717), a synthetic psilocybin formulation for treatment-resistant depression (TRD), showing that antidepressant effects observed at six weeks were maintained through six months — results that strengthen the company's NDA submission and bring it closer to what would be the first approved classic psychedelic in the US. The [COMP006](https://clinicaltrials.gov/study/NCT05624268) trial enrolled 581 patients across North America and Europe, a population with a mean current depressive episode duration exceeding three years and more than six lifetime episodes — a level of chronicity that makes demonstrating durable efficacy particularly difficult. In the 25 mg arm, 39% of participants achieved a clinically meaningful reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores — defined as a decrease of at least 25% — at week six, and this benefit was maintained on average through week 26. Among week-six responders who underwent retreatment in the blinded Part B period, nearly 30% subsequently achieved remission (MADRS ≤12). The 39% responder rate at week six compares favorably to the 25% observed in the companion trial COMP005, which used a single dose rather than two doses three weeks apart, suggesting a dose-number effect. **Competitive context** The most relevant approved comparator in TRD is Johnson & Johnson's Spravato (esketamine), an intranasal NMDA receptor antagonist that received its original FDA approval in 2019 and was expanded to monotherapy in January 2025. Cross-trial comparisons are inherently limited, but esketamine's clinical program targeted a less severely treatment-resistant population and requires administration in a certified healthcare setting under a Risk Evaluation and Mitigation Strategy program. COMP360, if approved, would also require supervised administration given the psychedelic experience, but the infrequent dosing schedule — potentially just a few sessions per year — represents a meaningfully different treatment model. Oral augmentation agents approved for MDD, including AbbVie's Vraylar (cariprazine) and Johnson & Johnson's Caplyta (lumateperone), are not approved specifically for TRD and require daily administration alongside a background antidepressant. The durability finding matters because TRD is a relapsing condition and short-lived responses have limited clinical utility. The consistency of the six-month durability signal across both COMP005 and COMP006 — two independently powered, randomized, blinded trials — provides a level of reproducibility that is unusual in psychedelic research and addresses one of the sector's persistent credibility challenges. Safety data remained consistent with earlier readouts - mainly transient and occurring on the day of dosing. Compass is conducting a rolling [NDA submission with the US FDA](https://allsci.com/news/approvals/fda-points-way-forward-for-compass-pathways-psilocybin-in-treatment-resistant-depression/), with final submission targeted for Q4 2026. A commercial launch is anticipated in the first half of 2027, contingent on FDA approval and Drug Enforcement Administration rescheduling of psilocybin from Schedule I. The company also holds FDA Breakthrough Therapy Designation for COMP360 in TRD. A parallel Phase II/III program in PTSD remains active, a population where no approved psychedelic-assisted therapy currently exists. The six-month data from COMP006 do not resolve the DEA rescheduling question, which remains an independent and potentially significant variable in the commercial timeline. However, the clinical package now rests on two positive, large-scale Phase III trials with consistent efficacy and safety profiles — a regulatory foundation that few investigational psychiatric drugs have achieved. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/comp360-psilocybin-treatment-resistant-depression)