Compass Pathways Hits Milestone in Psychedelic Drug Development with Phase 3 Psilocybin Readout for 250+ Patients
- Marc Violo
- Jun 23
- 3 min read
Compass Pathways has become the first company to publish Phase 3 data for a classical psychedelic. Its synthetic psilocybin candidate, COMP360, showed a statistically significant 3.6-point improvement over placebo on the MADRS scale at week 6 in patients with treatment-resistant depression (TRD). The MADRS (Montgomery–Åsberg Depression Rating Scale) is a widely used clinical tool that measures the severity of depressive symptoms on a 0–60 scale, where higher scores indicate more severe depression.
The trial enrolled 258 patients across 32 U.S. sites. Patients received a single 25mg dose of COMP360 or placebo, alongside psychological support. The company framed the results as modest but meaningful—especially considering the challenging treatment-resistant depression (TRD) population and the trial’s placebo-controlled design, which increases the risk of functional unblinding.
Safety Signal Matters More Than Efficacy
While the efficacy data drew headlines, the more important takeaway may be the clean safety readout. According to Compass, the Data and Safety Monitoring Board (DSMB) found no new or unexpected safety issues and no meaningful imbalance in suicidality between the treatment arms in either of the company's ongoing Phase 3 trials.
This was particularly notable given prior concerns: in its Phase 2b study, suicidal ideation and self-injury in the 25mg group raised eyebrows. Compass leadership underscored that these are features of TRD itself, not necessarily caused by the treatment.
The DSMB’s positive assessment clears a key regulatory hurdle. Compass executives have framed COMP005 as primarily a safety study, with efficacy viewed as a "bonus." Their goal is now to use this safety data to strengthen discussions with the FDA and prepare the ground for regulatory submission.
What the Numbers Mean
A 3.6-point difference on the MADRS is similar to that of esketamine (Spravato), which was approved with a 3-4 point placebo-adjusted improvement. Importantly, Compass tested a single dose in COMP005; its ongoing COMP006 study will examine whether two doses can achieve a greater magnitude and durability of effect.
The company is also positioning COMP360 as potentially more commercially viable than existing treatments. Unlike Spravato, which requires frequent administration, Compass believes its dosing model—possibly as few as two sessions—could appeal to patients and providers.
All Eyes on the Upcoming Research
Compass’ larger Phase 3 trial, COMP006, is underway with 568 patients across 96 sites in North America and Europe. It uses a three-arm design, evaluating one or two doses of psilocybin vs. placebo. This trial is expected to provide more definitive efficacy data and is scheduled to read out in the second half of 2026.
Engagement with trial sites is reportedly high. Company executives hope the positive data from COMP005 will accelerate recruitment and boost morale across participating investigators.
The company also plans to share the new data with the FDA shortly, but is holding off on immediate engagement with European regulators. The U.S. remains its primary target for now, although plans for PTSD studies and additional indications are advancing.
Preparing for Commercial Launch
With COMP360 now in late-stage development, Compass is shifting gears toward commercial readiness. The company has already announced partnerships with Greenbrook TMS, HealthPort, and Hackensack Meridian Health to begin shaping its delivery model. New job postings across manufacturing, supply chain, and commercial operations indicate that launch planning is ramping up.
If approved, Compass will face the challenge of introducing a new treatment paradigm that integrates psychedelic therapy into mainstream psychiatry. Psychological support is a key component of the intervention, meaning infrastructure and clinician training will be crucial.
At the same time, competition is rising. Shorter-acting psychedelic compounds from other biotech companies could complicate Compass’ market entry in the years ahead.
Still, today’s readout goes a long way in derisking COMP360’s path forward. With two successful readouts behind it—Phase 2b and COMP005—and a third, COMP006, on the horizon, Compass is now closer than ever to making psilocybin therapy a regulated treatment option for patients with few remaining alternatives.
