DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF PARTICIPANTS RECEIVING COMP360 PSILOCYBIN TREATMENT FOR TREATMENT-RESISTANT DEPRESSION ACROSS TWO PIVOTAL PHASE 3 TRIALS

The ongoing COMP 005 and COMP 006 trials are the largest double-blind, randomized-controlled trials of psilocybin conducted to date, and the first classic psychedelic trials to report Phase 3 data. Here we describe the demographic and clinical characteristics of the enrolled trial population. Participants aged ≥18 years with treatment-resistant depression (TRD, defined as a failure to respond to two, three or four different protocol-defined pharmacological treatments taken at an adequate therapeutic dose for at least 8 weeks) were recruited from outpatient settings. Medical records, validated methods of assessment and centralised medical monitor review were used to ensure eligibility. A Montgomery-Åsberg Depression Rating Scale (MADRS, performed by independent raters) total score ≥20 at Screening and Baseline was required to ensure at least moderate depression severity. Prior psychedelic use was capped to ensure the enrolled participants do not reflect more than real world population level usage. Participants taking antidepressant or antipsychotic medications at Screening were required to complete medication washout at least two weeks before Baseline. In COMP 005 participants were randomized 2:1 to receive 25 mg COMP360 or placebo, and in COMP 006 participants were randomized 2:1:1 to 25 mg, 10 mg or 1 mg COMP360 (Compass Pathways’ proprietary, synthetic psilocybin formulation). In total 258 (54.3% female; mean age [standard deviation] 45.7 [13.7]) and 581 (51.1% female; mean [SD] age 45.2 [13.4]) were randomized and received study drug in COMP 005 and COMP 006, respectively. Approximately one-third of participants had failed 3 or more pharmacological treatments in the current episode (COMP 005 30.6%; COMP 006 31.8%). Approximately two-thirds (COMP 005 57.8%; COMP 006 62.1%) had a Baseline MADRS score of ≥31 indicating severe depressive symptoms. The mean duration of the current depressive episode amongst participants was 36.0 [31.1] and 41.8 [42.5] months, with a mean number of lifetime depressive episodes of 7.5 [9.9] and 6.2 [8.7] denoting the chronic and recurrent nature of TRD and the severity of the population enrolled. Over two-thirds of participants required washout of medications during the screening period (COMP 005 67.4%; COMP 006 76.8%). Prior use of any classic psychedelics, including psilocybin was low in both trials (COMP 005 5.4%; COMP 006 and 6.4%). These data demonstrate that the COMP360 Phase 3 trial populations are broadly in line with other clinical trials of TRD with respect to demographic and clinical characteristics. The trials capture a notably severe cohort, reflected in the high number of lifetime depressive episodes and the chronicity of the current episode. The requirement for at least 8 weeks of antidepressant treatment—exceeding the thresholds typically used in TRD trials—and the confirmation of these failures via medical records further strengthen the rigor and credibility of the severity classification. Notably, many participants had failed other pharmacological and non-pharmacological interventions that were not protocol defined treatment failures, indicating that the number of failures underestimates the actual degree of treatment resistance. Lifetime use of psychedelics was low indicating the representativeness of the trial population. Once completed, these pivotal trials will provide valuable data on durability of effects, and the safety and efficacy of repeat dosing over 52 weeks.