Synthetic Psilocybin Improves Symptom Severity in Treatment-Resistant Depression
- Adjuva Psychiatry
- 3 days ago
- 2 min read
Findings showed COMP360 psilocybin 25mg statistically significantly reduced symptom severity compared with the 1mg dose at week 6.
Top line data were announced from a phase 3 study evaluating COMP360, a synthetic, proprietary formulation of psilocybin, in patients with treatment-resistant depression (TRD).
The randomized, fixed repeat dose, double-blind phase 3 COMP006 study (ClinicalTrials.gov Identifier: NCT05711940) evaluated the efficacy, safety, and tolerability of COMP360 psilocybin in patients aged 18 years and older with TRD. The study consists of 3 parts: a 9 week blinded period (Part A), an extension phase through week 26 (Part B), and an open-label treatment phase from week 26 to week 52 (Part C).
Study participants (N=581) were randomly assigned 2:1:1 to receive 2 administrations of COMP360 psilocybin in doses of 25mg (n=296), 10mg (n=142) or 1mg (n=143), taken 3 weeks apart. The primary endpoint was the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at 6 weeks.
Findings showed COMP360 psilocybin 25mg statistically significantly reduced symptom severity, as measured by MADRS, compared with the 1mg dose at week 6 (mean difference, -3.8 points [95% CI, -5.8, -1.8]; P <.001). Notably in the 25mg arm, 39% of patients achieved a clinically meaningful MADRS reduction of 25% or greater; improvements were seen as early as 1 day post-administration and were sustained through 6 weeks.
The most common treatment-emergent adverse events were headache, nausea, anxiety and hallucination. Most events occurred on the days of administration and were resolved within a day.
These findings are consistent with previously reported results from Part A of the COMP005 study (ClinicalTrials.gov Identifier: NCT05624268), which demonstrated that COMP360 psilocybin 25mg significantly improved depression symptom severity vs placebo.
Updated Part B results demonstrated sustained efficacy for COMP360 psilocybin 25mg, maintaining symptom severity reductions through week 26 after just 1 or 2 doses. Notably, greater than 40% of participants who achieved a clinically meaningful reduction in MADRS total score but remained not remitted by 6 weeks went into remission after a second dose.
“TRD patients have extremely limited treatment options, and the unmet need remains profound,” said Dr Guy Goodwin, Chief Medical Officer at Compass Pathways. “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 1 or 2 doses lasted at least through 26 weeks, alongside a well tolerated safety profile.”
According to Compass Pathways, a New Drug Application submission is expected to be completed in the fourth quarter of 2026.
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