Compass Pathways Delivers Two Positive Phase 3 Results for Psilocybin in Depression
Compass Pathways just gave the psychedelic medicine field its biggest day in years. On February 17, the company reported that both of its Phase 3 trials of COMP360 psilocybin met their primary endpoints for treatment resistant depression. Shares surged more than 30%. Then, on a live webcast, management revealed the data behind the headlines, including MADRS response curves, demographic breakdowns and durability signals that paint a far more detailed picture than the morning press release offered.
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| Key Takeaway | Details |
|---|---|
| COMP006 Primary Endpoint | Met with high statistical significance (p<0.001) |
| MADRS Score Difference (COMP006) | Mean reduction of 3.8 points, 25 mg vs. 1 mg at Week 6 |
| MADRS Score Difference (COMP005) | Mean reduction of 3.6 points, 25 mg vs. placebo at Week 6 |
| Absolute MADRS Change from Baseline (COMP006, 25 mg) | 7.6 points |
| Absolute MADRS Change from Baseline (COMP005, 25 mg) | 4.9 points |
| COMP006 Response Rate (25 mg) | 39% achieved clinically meaningful improvement at Week 6 |
| COMP005 Response Rate (25 mg) | 25% achieved clinically meaningful improvement at Week 6 |
| 10 mg Arm Performance | Showed a larger effect than expected, converging with 25 mg at multiple timepoints |
| Durability | COMP005 responders maintained benefit through at least Week 26 |
| Safety Profile | Well tolerated; suicidal ideation SAEs below 1% across both trials |
| NDA Submission Target | Q4 2026 via rolling submission |
| Total Participants Dosed | More than 800 across both trials |
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The MADRS Curves Tell the Real Story
The webcast offered something the press release could not: visual evidence of how COMP360 performs over time. In COMP005, the 25 mg dose outperformed placebo at every measured timepoint. The separation appeared the day after dosing and held through Week 6. However, the confidence intervals between arms narrowed considerably by that sixth week.
The absolute change from baseline revealed a notable gap between the two studies. In COMP005, the 25 mg arm dropped 4.9 points on the MADRS. The placebo arm dropped just 1.2 points. In COMP006, the numbers were larger across the board. The 25 mg arm fell 7.6 points, the 10 mg arm fell 6.3, and the 1 mg arm fell 3.7. The two dose regimen in COMP006 appears to produce a stronger overall response.
The 10 mg Surprise
One of the more interesting findings involved the 10 mg dose. In Compass’s earlier Phase 2b study, 10 mg failed to show meaningful efficacy. This time, it performed better than expected. At multiple timepoints, the 10 mg arm converged with the 25 mg arm. Chief Medical Officer Guy Goodwin acknowledged the shift but noted that the effect size at Week 6 still fell below the 3 point MADRS threshold often considered clinically significant.
The 10 mg performance also raised a question analysts pressed on during the Q&A: could there be a ceiling effect with dosing? Goodwin was candid. The company does not yet know the answer but hopes to learn more from the full dataset.
Durability and the Second Dose Question
The 26 week data from COMP005 added critical context. Goodwin called the results remarkable because they showed persistent treatment effects from just one or two 25 mg doses over six months. Participants who responded at Week 6 largely maintained their improvement.
The company also highlighted that more than 40% of initial responders who had not yet reached remission went on to remit after a second dose. That sounds compelling in a press release. On the webcast, however, the underlying numbers came into sharper focus. That figure represents roughly 13 participants out of 31 initial responders and partial responders. It is meaningful data, but the small sample size warrants caution.
An important caveat applies to all long term data from COMP005. Participants were allowed to start oral antidepressants during Part B of the trial. Goodwin said the company does not yet have data on how many did so.
Safety Holds Steady
Across both trials, COMP360 showed a safety profile consistent with earlier studies. Most side effects resolved within 24 hours. They included headache, nausea, anxiety and visual effects. In the 25 mg arm of COMP006, 24% of participants experienced an adverse event lasting more than two days, which Goodwin attributed to the two dose design.
The suicidality data drew close attention. Serious adverse events involving suicidal ideation occurred at rates below 1% in both studies. The single instance of suicidal behavior in the entire program occurred in the 1 mg control arm, not the treatment arm.
What Comes Next
Compass has requested an FDA meeting to discuss a rolling NDA submission. The company targets a filing by the end of 2026. If approved, COMP360 would become the first psilocybin therapy cleared by the agency.
On the commercial side, Chief Commercial Officer Lori Englebert positioned COMP360 against Spravato, the only currently approved TRD medication. She noted that Johnson & Johnson failed to demonstrate efficacy in some of its own TRD trials, underscoring how difficult this patient population is to treat.
The label remains an open question. Analysts asked how dosing guidance might look. Englebert suggested it could include a one or two dose induction phase with less prescriptive direction on subsequent retreatment. Steve Levine, the company’s Chief Patient Officer, agreed.
Goodwin also hinted at a future beyond pure pharmacology. He said the company expects to see innovation around the therapeutic container after approval. Whether more active psychotherapy following administration might enhance outcomes remains an open research question, but Levine suggested it is one many in the field intuitively believe deserves exploration.
For the millions of Americans living with treatment resistant depression, today’s data represents something concrete: two positive Phase 3 trials, a path toward FDA review and growing evidence that psilocybin can deliver rapid, durable relief where conventional treatments have failed.
