Compass Pathways Reports Positive Phase 3 Results for COMP360 in Treatment-Resistant Depression

Compass Pathways reported positive Phase 3 results for its investigational psychedelic COMP360 in treatment-resistant depression, with the 25 mg dose showing statistically significant improvements in depression scores and signs of durability through 26 weeks. The company's stock rose 31% from $5.81 at market close on 13 February to $7.63 on 17 February following the announcement.

The company reviewed two Phase 3 studies: COMP005, a placebo-controlled trial evaluating a single 25 mg administration of COMP360 with a primary endpoint at six weeks, and COMP006, a three-arm study evaluating 10 mg and 25 mg doses, with two administrations given three weeks apart and a six-week primary endpoint.

In COMP005, the company previously released results showing a 3.6-point difference on the Montgomery–Åsberg Depression Rating Scale (MADRS) between the 25 mg group and placebo at week six. The separation was statistically significant at every reported time point, starting the day after administration (day 2) and continuing through the six-week primary endpoint.

In COMP006 Part A, the company reported statistically significant separation at every time point starting the day after administration through week six. At week six, the trial showed a 3.8-point difference on MADRS between the 25 mg group and a 1 mg active comparator. Patients received two doses of COMP360 at the start of the trial and at three weeks.

COMP360 also triggered a clinically meaningful MADRS score reduction – classified as a 25% decrease from baseline or more – in 39% of patients at week six. Of these patients, all experienced a statistically significant rapid onset of benefit from the day after administration. COMP360 maintained its impact across all measured timepoints through to week six.

New data from the COMP005 study uncovers the durability of COMP360's efficacy, as 25% of patients in the 25 mg cohort achieved clinically meaningful MADRS reductions through 26 weeks after one or two doses. The company discussed longer-term follow-up from COMP005 Part B, which extends to week 26 and allows for up to one retreatment while maintaining blinding.

The 26-week data indicated that a subset of patients maintained clinically meaningful benefit with one or two treatments through at least six months. Among patients who received a second administration, 40% subsequently entered remission. The company described an overlay comparison of the first six weeks of COMP005 and COMP006, saying the 25 mg curve appeared "remarkably consistent" from baseline through week three and then showed further benefit after the second administration at week three in COMP006.

The company defended the use of a 25% MADRS reduction as a marker of clinical meaningfulness, stating it was based on published "crosswalk" work in an esketamine (Spravato) dataset linking changes in MADRS with other measures such as the Clinical Global Impressions-Severity (CGI-S), PHQ-9, and Sheehan Disability Scale. Using an average baseline MADRS around 32, a six-point improvement corresponds to roughly a 25% reduction.

The psychedelic was proven to be safe and tolerable in both the COMP005 and COMP006 trials, with eight (5%) and six (2%) patients experiencing severe treatment-emergent adverse events (TEAE), respectively, during each study. The most common TEAEs across both studies were headache, nausea, anxiety and visual hallucination.

Compass is centering its regulatory filing and planned launch on the 25 mg dose, reports constructive engagement with the FDA, and expects a commercial safety framework similar to the Spravato REMS, while the 10 mg option remains a secondary consideration. The company plans to submit a new drug application (NDA) for COMP360 in Q4 2026 and is hoping to be commercially ready by the end of 2026.

If approved, COMP360 would likely become the first classic psychedelic to get the regulatory greenlight for the treatment of a mental health condition. This comes after Lykos Therapeutics' midomafetamine (MDMA) therapy for post-traumatic stress disorder (PTSD) missed out on achieving this milestone due to trial design concerns.

Previous data from the COMP005 trial, released in June 2025, was met with hesitancy. While the study met its primary endpoint, the data was not as strong as Compass had hoped, which saw the biotech's stock value drop more than 50%.