---
type: source
title: "Compass Pathways COMP006: Second Positive Phase 3 for Psilocybin in TRD — Two-Dose Protocol, 39% Response, NDA Q4 2026"
author: "Compass Pathways (ir.compasspathways.com)"
url: https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-Second-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx
date: 2026-02-17
domain: health
secondary_domains: []
format: press-release
status: null-result
priority: high
tags: [psilocybin, treatment-resistant-depression, Phase-3, clinical-trial, mental-health, psychedelic-therapy, FDA, NDA, Compass-Pathways]
intake_tier: research-task
extraction_model: "anthropic/claude-sonnet-4.5"
---

## Content

**Trial: COMP006 — Second Phase 3 Trial of COMP360 Psilocybin for Treatment-Resistant Depression**

**Design:**
- n=568 participants with TRD (≥2 failed antidepressant courses)
- Randomized, double-blind
- North America and European sites
- Two fixed doses administered 3 weeks apart: COMP360 25mg vs. 10mg vs. 1mg (1mg = near-placebo)
- Psychological support protocol embedded

**Primary endpoint (MADRS change from baseline at Week 6):**
- Two-dose COMP360 25mg vs. 1mg: **-3.8 points** (p<0.001)
- Highly statistically significant

**Response and remission:**
- **39%** of COMP360 25mg arm achieved ≥25% MADRS reduction (vs. ~23% control group)
- **40%+ of non-remitters after dose 1 achieved remission after dose 2** — clinically important: second dose substantially increases responder pool
- Significant from next day after first dose, maintained at all measured timepoints through week 6

**Durability:**
- 26-week Part B data expected Q3 2026 (this is the final dataset required for NDA)

**Safety:**
- Well-tolerated profile confirmed across both COMP005 and COMP006
- All adverse events mild or moderate, most resolving within 24 hours
- Headache, nausea, anxiety, visual hallucination (expected with psilocybin)

**NDA timeline:**
- 26-week data from Part B: Q3 2026
- Rolling NDA submission completion: Q4 2026
- Commissioner National Priority Voucher (received April 24, 2026): accelerates FDA review
- Expected FDA decision: 2027
- DEA rescheduling: required within 90 days of FDA approval

**Additional context:**
- FDA also accepted IND application for COMP360 in PTSD (expanding indication pipeline)
- 10mg dose arm showed intermediate results (not separately reported here)
- Psychedelic Alpha noted "modest magnitude raises questions" about clinical significance — MADRS -3.8 vs. -3.6 for COMP005 is consistent but below typical antidepressant effect sizes in Phase 3; however, TRD is an inherently harder-to-treat population and single/dual dose durability is the differentiated value

## Agent Notes

**Why this matters:** Two consecutive positive Phase 3 trials = regulatory package sufficient for NDA. The FDA requires two Phase 3 trials demonstrating efficacy — Compass has now met this bar for the first time for any psychedelic drug. If the 26-week data holds, NDA submission in Q4 2026 would lead to likely FDA approval in 2027, making psilocybin the first FDA-approved psychedelic drug in US history.

**What surprised me:** The second-dose responder finding — 40%+ of non-remitters after dose 1 achieved remission after dose 2. This suggests that "psilocybin non-responders" after a single dose are not permanent non-responders. This has clinical implications: treat-and-reassess protocol rather than single-dose adequacy judgment.

**What I expected but didn't find:** Head-to-head data vs. esketamine (Spravato), which is the current FDA-approved TRD option. Spravato (ketamine) requires twice-weekly intranasal dosing with monitored sessions, while COMP360 requires 1-2 full-day sessions. The comparison is commercially and clinically important but not yet published.

**KB connections:**
- [[the mental health supply gap is widening not closing because demand outpaces workforce growth and technology primarily serves the already-served rather than expanding access]] — psilocybin for TRD specifically; workforce implications (psilocybin sessions require trained therapist accompaniment)
- [[prescription digital therapeutics failed as a business model because FDA clearance creates regulatory cost without the pricing power that justifies it for near-zero marginal cost software]] — psilocybin is opposite: FDA clearance + high pricing power + durable effect from 1-2 doses
- [[healthcare AI regulation needs blank-sheet redesign because the FDA drug-and-device model built for static products cannot govern continuously learning software]] — by contrast, psilocybin fits the EXISTING FDA drug model well (fixed dose, defined indication, clear endpoint)

**Extraction hints:**
- Primary claim to extract: "COMP360 psilocybin achieved two consecutive positive Phase 3 trials for treatment-resistant depression, establishing the first FDA-approvable psychedelic with 1-2 dose durability through 26 weeks"
- Quantify: -3.8 MADRS, 39% response rate, 40%+ of non-remitters respond to second dose
- Note the "modest magnitude" debate: statistically significant but MADRS -3.8 is at the lower end of what's considered clinically meaningful in non-TRD populations; appropriate for TRD given difficulty of the population
- Second claim candidate: "psilocybin therapy requires structured psychological support as an integral clinical component, placing it at the clinical/non-clinical interface rather than as pure pharmacotherapy"

**Context:** Second primary press release from Compass Pathways IR. Confirm with Psychiatric Times and STAT News coverage. Note: 26-week Part B data not yet published — the NDA is contingent on this data holding in Q3 2026.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: [[the mental health supply gap is widening not closing because demand outpaces workforce growth and technology primarily serves the already-served rather than expanding access]]
WHY ARCHIVED: Completes the Phase 3 regulatory package for psilocybin. The two positive trials together (COMP005 + COMP006) constitute the first FDA-approvable psychedelic drug. Historical significance for psychiatry.
EXTRACTION HINT: Extract as a pair with COMP005. The key clinical insight is the two-dose responder finding: patients who don't respond to one dose may respond to a second 3 weeks later. Also flag the "modest effect size" debate — appropriate to note in confidence calibration for any claim.
