DURABILITY OF EFFICACY AND SAFETY OF COMP360 PSILOCYBIN FOR TREATMENT-RESISTANT DEPRESSION (TRD) ACROSS 26 WEEKS IN A DOUBLE-BLIND, RANDOMIZED, CONTROLLED PHASE 3 STUDY

Introduction

COMP360 is a novel, proprietary, synthetic formulation of psilocybin being investigated for treatment-resistant depression (TRD) and post-traumatic stress disorder. COMP 005 is a multi-center, randomized, double-blind, placebo-controlled phase 3 study of the efficacy, safety, and tolerability of COMP360 monotherapy in adults with TRD. Here, we investigate the safety and efficacy of 1 or 2 administrations of 25 mg COMP360 compared to placebo across the 26-week double-blind period of COMP 005.

Methods

Adult participants were enrolled in COMP 005 after meeting eligibility criteria, including presence of TRD as defined as having experienced 2–4 inadequate responses to prior treatments during their current depressive episode. In Part A (6 weeks), participants were randomized in a 2:1 ratio to receive a single administration of either COMP360 25 mg or placebo. The primary efficacy endpoint was change from baseline MADRS total score at Week 6. Part B was a 20-week continuation of COMP 005 in which participants were potentially eligible for a second administration of their originally assigned treatment if they did not achieve remission at Week 6 or, if they did achieve remission and subsequently met relapse criteria during Part B. In the current analysis, descriptive statistics are provided for change from baseline in MADRS total score at Weeks 10, 14, 18, 22 and 26.

Results

258 participants were randomized and dosed with either COMP360 25 mg (n=171) or placebo (n=87). Least square mean (LSM) change from baseline MADRS total score was significantly greater in participants receiving a single administration of COMP360 than in those receiving placebo at all time points measured during Part A, as early as the day after administration [LSM Difference (95% confidence interval): Day 2: -4.7 (-7.0, -2.3), p < 0.001; Week 1: -7.2 (-9.6,-4.8), p < 0.001; Week 3: -5.2 (-7.4,-2.9), p < 0.001; Week 6: -3.6 (-5.7, -1.5), p < 0.001]. During Part B, numerical separation from placebo was maintained across an additional 20 weeks (no statistical analyses performed as prespecified in the Statistical Analysis Plan). 70% of participants in the COMP360 25 mg and 53% of participants in the placebo arm received a second administration during Part B. The most common treatment-emergent adverse events (TEAEs) were headache, nausea, hallucination (visual), and anxiety. Most TEAEs in the 25 mg arm occurred on the days of administration (66%), with the majority of these events (88%) resolving within a day. There were 13 treatment-emergent serious adverse events (SAEs) from 10 participants (3.9%) overall; 8 (4.7%) in the COMP360 25 mg arm and 2 (2.3%) in the placebo arm.

Conclusions

Reductions in MADRS total scores following one or two administrations of COMP360 25 mg were sustained for at least 26 weeks. In Part B, these longer-term changes were numerically > those in the placebo-treated arm.. These data support sustained durability of antidepressant effect of 1 or 2 administrations of COMP360 25 mg.