COMP360 Psilocybin Meets Primary Endpoint in Second Phase 3 Trial for TRD

On February 17, 2026, Compass Pathways announced that its investigational synthetic psilocybin formulation, COMP360, met the primary endpoint in the second pivotal phase 3 trial evaluating the therapy in adults with treatment-resistant depression (TRD).¹ In the COMP006 study, two 25-mg doses administered 3 weeks apart produced a statistically significant reduction in depressive symptom severity at week 6 compared with a 1-mg dose control, reinforcing findings from the companion COMP005 trial and advancing the program toward regulatory submission.

“These results redefine rapidity and durability for TRD patients with onset as early as the next day and, for those who respond, effects from just one or two doses lasted at least through 26 weeks, alongside a well-tolerated safety profile,” said Guy Goodwin, MD, chief medical officer at Compass Pathways, in a statement.¹

COMP360 is a synthetic formulation of psilocybin, a classic serotonergic psychedelic that acts primarily as a 5-HT2A receptor agonist. Psychedelic compounds are hypothesized to induce rapid antidepressant effects through modulation of cortical network connectivity and promotion of neuroplasticity, in conjunction with structured psychological support.

In COMP006, the primary endpoint was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6. The least squares mean difference between the 25-mg and 1-mg groups was –3.8 points (95% CI, –5.8 to –1.8; P <.001).¹ In total, 39% of participants in the 25-mg arm achieved a ≥ 25% reduction in MADRS score at week 6.

The company also reported statistically significant separation from the comparator beginning the day after administration, with effects maintained through week 6. Longer-term data from Part B of COMP006, extending through week 26, are expected later in Q3 of 2026.¹

The parallel COMP005 trial, a randomized, double-blind, placebo-controlled study conducted in 258 participants in the United States, previously demonstrated a –3.6-point mean treatment difference on the MADRS at week 6 for a single 25-mg dose versus placebo (95% CI, –5.7 to –1.5; P <.001). Among participants achieving a ≥ 25% MADRS reduction at week 6, the durability of effect was reported through week 26 after 1 or 2 doses.¹ Full phase 3 datasets have not yet been published in a peer-reviewed journal.

Estimates suggest that approximately 30% of patients with major depressive disorder (MDD) meet criteria for TRD, representing millions of adults in the United States.² Patients with TRD experience higher functional impairment, increased health care utilization, and elevated suicide risk compared with those with treatment-responsive depression.²

Current FDA-approved pharmacologic options specifically indicated for treatment-resistant depression (TRD) remain limited. These include adjunctive aripiprazole, brexpiprazole, and quetiapine, as well as esketamine nasal spray. Nonpharmacologic interventions include electroconvulsive therapy and repetitive transcranial magnetic stimulation.³ COMP360 appears to be the first psychedelic therapy to consistently demonstrate a highly statistically significant improvement in MADRS scores across controlled trials.

Across COMP005 and COMP006, treatment-emergent adverse events were reported as generally mild to moderate and most commonly occurred on dosing days. Frequently reported events included headache, nausea, anxiety, and visual hallucination. Serious adverse events were reported in 5% of participants in COMP005 and 2% in COMP006; the suicidal ideation rate was < 1% across studies, with 1 suicidal behavior event occurring in the 1 mg arm of COMP006. An independent Data Safety Monitoring Board did not identify new or unexpected safety signals based on available data.

COMP360 has received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for TRD.¹ Compass Pathways has requested a meeting with the FDA and anticipates submitting a New Drug Application in Q4.

Detailed subgroup analyses, remission rates, functional outcomes, and comprehensive long-term safety data are pending. If confirmed through regulatory review and peer-reviewed publication, the COMP360 program would represent a novel therapeutic modality in TRD, characterized by limited dosing sessions and rapid onset of antidepressant effect.

“Across three robust, well-designed and well-executed clinical trials involving more than 1,000 participants, we have now demonstrated consistent, highly statistically significant results at the primary endpoint and a clinically meaningful effect,” said Compass Pathways Chief Executive Officer Kabir Nath, MBA, in a statement. “This is a remarkable achievement for the field of psychiatry—especially in the TRD population, where proving benefit has historically been extraordinarily challenging.”

References

1. Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression. Compass Pathways. Published on February 17, 2026. Accessed on February 19, 2026. 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

2. McIntyre RS, Alsuwaidan M, Baune BT, et al. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023;22(3):394-412. doi:10.1002/wps.21120

3. Treatment-Resistant Depression. Cleveland Clinic. Published on May 16, 2023. Accessed on February 19, 2026. https://my.clevelandclinic.org/health/diseases/24991-treatment-resistant-depression

4. US Food and Drug Administration. Breakthrough Therapy designation. https://www.fda.gov/drugs/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy