BREAKING: Second positive Phase 3 for Compass psilocybin with modest magnitude raises questions about dosing benefit

Compass Pathways reports a positive topline readout from its second Phase 3 trial of synthetic psilocybin (COMP360) for treatment-resistant depression (TRD), based on the COMP006 study (N=581). COMP006 tested two doses given 3 weeks apart at 1 mg, 10 mg, or 25 mg, and the primary 6-week endpoint compares MADRS change from baseline between the 25 mg and 1 mg groups. The company also provides 26-week data from its earlier smaller Phase 3 trial (COMP005, N=258). Psychedelic Alpha notes the outcome is positive and safety appears consistent with expectations, but the effect size looks modest relative to prior signals. The comparison structure differs from COMP005 (25 mg vs placebo), leaving questions about the incremental benefit of a second dose, how much deeper response may be, and whether patients who do not respond to an initial dose will benefit from additional dosing.