お知らせ • Dec 02
Compass Pathways Announces Further Positive Results from Phase IIb Trial of Investigational Comp360 Psilocybin Therapy for Treatment-Resistant Depression
COMPASS Pathways plc announced further results from its phase IIb clinical trial of COMP360 psilocybin therapy for treatment-resistant depression. Additional analyses of primary and secondary endpoints validated topline findings and provided more insights into safety data. Analyses of exploratory measures including anxiety, self-reported depression, positive and negative affect, and functioning, showed greater improvements for patients receiving a 25mg dose of COMP360 psilocybin compared with those receiving a 1mg dose after three weeks, both with psychological support. Further analysis is ongoing and full trial results will be submitted for publication in a peer-reviewed journal. The data will be reviewed with regulators early next year. The objective of the trial was to find the appropriate dose for a larger, pivotal phase III programme, which COMPASS expects to begin in 2022. COMPASS reported topline data from this trial last month, which investigated three doses of COMP360 psilocybin in 233 patients with TRD. The results showed that a single 25mg dose of COMP360 demonstrated a highly statistically significant and clinically relevant reduction in depressive symptom severity after three weeks, with a rapid and durable treatment response. The 25mg group vs the 1mg group showed a -6.6 difference on the MADRS depression scale at week 3 (p<0.001). In the 25mg group, 36.7% (29 patients) showed response at week 3 and 29.1% were in remission at week 3. Furthermore, at the end of the trial at week 12, 24.1% were sustained responders. Additional analyses of primary and secondary endpoints have supported these results. As well as looking at clinician-rated depression severity on the MADRS, the trial explored other aspects which are recognised as being important for patients with TRD - and essential to recovery - including positive and negative affect, anxiety, self-rated depression severity, quality of life, functioning and cognition. These exploratory measures also showed that patients in the 25mg dose group of COMP360 psilocybin therapy reported benefits on those measures over those in the 1mg group. On the PANAS scale measuring positive and negative affect, patients in the 25mg group had a higher increase in positive affect and a greater decrease in negative affect on the day after COMP360 administration and at the questionnaire’s final administration at week 3. On scales measuring anxiety, self-rated depression and functioning (SDS and WSAS), a greater improvement was also shown at week 3, by patients in the 25mg group compared with the 1mg group. A post-hoc analysis of the 19 sustained responders in the 25mg group found that changes in quality of life, self-reported depression severity, and functioning, were clinically meaningful, with mean scores for these patients returning to “normal” levels and maintained to 12 weeks, the end of the trial. Durability is being studied in a one-year follow-up study which is currently underway. As noted in the topline data reported last month, COMP360 psilocybin was generally well-tolerated. Further analysis showed that there were no concerns with vital signs, ECG or clinical laboratory data in any of the treatment groups. The majority of treatment-emergent adverse events occurring on the day of COMP360 administration resolved on the same day or the day after (77.4%); most of these events were mild or moderate in nature, eg headache, nausea, fatigue. All TEAEs involving hallucination (which only occurred in the 25mg and 10mg groups) and illusion (which occurred in all groups) started on the day of administration and resolved on the same day. No events of this nature continued past the administration day. TEAEs of suicidal ideation, suicidal behaviour and intentional self-injury were seen in all groups, as is regularly observed in a TRD population. Two thirds of the patients had previous thoughts of wishing to be dead, as assessed by a suicidality scale completed during patient screening; this included all patients reporting one of these adverse events, so all patients who experienced these events during the trial had said in patient screening that they had suicidal thoughts prior to the trial. Further detailed case-by-case analysis of safety data found no evidence to suggest, at this time, a causal relationship between these reported adverse events and administration of COMP360. The events occurred in all treatment groups and at a range of onset times and durations; the majority occurred more than a week after the psilocybin session. There was no difference between the three groups post-administration in scores from item 10 on the MADRS, which measures suicidality and was assessed by a blinded remote rater; mean 27 of the TEAEs of suicidal ideation, suicidal behaviour and intentional self-injury occurred across 17 patients, with seven patients in the 25mg group, six in the 10mg group, and four in the 1mg group 14 of these events were reported as treatment-emergent serious adverse events; these occurred across nine patients, with four patients in the 25mg group, four patients in the 10mg group, and one in the 1mg group The majority of these TESAEs occurred at least one week after the COMP360 psilocybin session All suicidal behaviours occurred at least one month after the psilocybin therapy session and all patients reporting these events were non responders at their last assessment prior to the event or at the time of the event.
