COMP360 Psilocybin Therapy in Treatment-Resistant Depression: Results of a Large Randomized Controlled Phase IIb Monotherapy Study and an Exploratory Uncontrolled Adjunctive Therapy Study

Abstract: COMP360 is a synthetic purified form of psilocybin in development for treatment of adults with treatment-resistant depression (TRD). COMP360 psilocybin therapy combines oral COMP360 psilocybin with psychological support. Efficacy and safety of COMP360 psilocybin therapy in adults with TRD has been assessed in two clinical trials. The COMP001 monotherapy study (Nf233) is the largest randomized double-blind controlled trial of psilocybin therapy in participants with TRD to date, utilizing COMP360 psilocybin therapy doses of 25/10/1 mg. The COMP003 (Nf19) open-label trial explored COMP360 (25 mg) psilocybin therapy adjunctive to ongoing serotonergic antidepressants. The primary endpoint in both studies was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Week 3. Dose-dependent reductions in MADRS scores emerged in COMP001 beginning the day after the study drug session and persisted at Week 3, with COMP360 25 mg demonstrating statistical superiority over 1 mg. Rates of response and remission at Week 3 and sustained response at Week 12 were also higher for COMP360 25 mg than for 1 mg. Similar effects of COMP360 25 mg on MADRS and response/remission at Week 3 were observed in the COMP003 study. COMP360 25 mg was well-tolerated in both studies. >90% of TEAEs were mild/moderate in severity. A single administration of COMP360 25 mg with psychological support appeared to be efficacious and well-tolerated. The small open-label study suggests possible benefit as an adjunctive therapy to common antidepressants. Efficacy and safety of COMP360 25 mg should be further evaluated in larger controlled confirmatory studies.Short Description: COMP360 is a synthetic, purified form of psilocybin in development as an investigational compound for treatment of patients with treatment-resistant depression (TRD). COMP360 psilocybin therapy combines oral COMP360 administration with psychological support. Data from COMP001 monotherapy (Nf233) and COMP003 adjunctive therapy (Nf19) studies in adults with TRD are presented here. In both studies, COMP360 (25 mg) psilocybin therapy reduced depression symptomatology at the primary endpoint (Week 3) and was well-tolerated.Name of Sponsoring Organization(s): COMPASS Pathways, Inc