COMPASS Pathways Presents Largest Ever Study of Psilocybin Therapy

COMPASS Pathways plc recently presented positive data from the largest randomized, controlled, double-blind study of psilocybin therapy ever completed, at the American Psychiatric Association annual meeting in New Orleans. The study showed that a single 25-mg dose of COMP360 psilocybin, in combination with psychological support, was associated with a highly statistically significant reduction in depressive symptoms after 3 weeks (p<0.001), with a rapid and durable response for up to 12 weeks.

The randomized, controlled, double-blind Phase 2b clinical trial was designed to understand the efficacy and safety of a single dose of investigational COMP360 psilocybin (25 mg or 10 mg), compared to 1 mg in patients with treatment-resistant depression (TRD). 233 patients with TRD received either 1 mg, 10 mg, or 25 mg COMP360 psilocybin, in conjunction with psychological support from specially trained therapists. Symptoms of depression were assessed using the Montgomery-Åsberg depression rating scale (MADRS), a widely used and accepted scale for assessing depression; the MADRS assessments were made by an independent, blinded rater.

Key results:

• Depression symptoms: patients who received a 25-mg dose of COMP360 psilocybin with psychological support experienced a highly statistically significant reduction in symptoms of depression after 3 weeks: the difference between 25-mg group and 1-mg group was -6.6 on the MADRS depression scale at week 3, p<0.001.
• Durability: double the number of patients who received 25 mg had a sustained response at week 12, compared to those who received 1 mg (20.3% of patients in the 25-mg group vs 10.1% in the 1-mg group).
• Tolerability: COMP360 psilocybin was generally well-tolerated. On the day of COMP360 administration, headache, nausea, and dizziness were the only adverse events where a dose-related increase in incidence was evident and there were no clinically significant differences between dose group in vital signs or clinical laboratory tests observed during the study.
• Adverse events: In this study suicidal ideation and intentional self-injury were seen in all treatment groups (as is regularly observed in a TRD population), and the majority occurred more than a week after the psilocybin session. There was no mean worsening of suicidal ideation scores in any treatment group. Suicidal behaviors were reported at least 1 month after COMP360 administration for 3 non-responders in the 25mg arm.

David J Hellerstein MD, a Principal Investigator on the trial and Professor of Clinical Psychiatry at the Columbia University Irving Medical Center, said “Treatment-resistant depression is one of the biggest challenges we face in psychiatry, and chances of success decreases with each treatment that a patient tries. It’s rare to see such positive outcomes of clinical trials in this disease area, which is why these results are so significant. I hope this represents a major step in finding new options for people living with treatment-resistant depression.”

Dr Guy Goodwin, Chief Medical Officer, COMPASS Pathways, added “Our mission is all about developing mental health innovations through scientific evidence, which is why we’re so honoured to present the largest study of its kind at the APA. In this study, a significant number of patients experienced improvement in their symptoms of depression after just a single dose of 25-mg psilocybin with psychological support, with effects lasting for up to 3 months of the study. We now need to continue our research to understand if this can be replicated in even larger trials.”

More than 320 million people globally suffer with major depressive disorder (MDD), the leading cause of disability worldwide and one of the fastest growing mental health illnesses. About a third of these patients – 100 million people – aren’t helped by existing therapies and suffer with treatment-resistant depression (TRD). As many as 30% of these attempt suicide at least once during their lifetime. TRD carries two to three times the medical costs of a non-TRD MDD patient, and patients with TRD have a higher all-cause mortality compared with non-TRD MDD patients. The TRD population is by definition more difficult to treat and more likely to relapse than patients with major depressive disorder. In 2018, COMPASS received FDA Breakthrough Therapy designation for its COMP360 psilocybin therapy for TRD.

This randomized, controlled, multicenter, double-blind Phase 2b trial is the largest psilocybin therapy clinical trial ever conducted, with 233 patients from 10 countries in North America and Europe. 94% of the patients had no prior experience with psilocybin. The objective of the trial was to find the appropriate dose for a larger, pivotal Phase 3 program, which COMPASS expects to begin in 2022.

The trial assessed the safety and efficacy of COMP360 psilocybin therapy at three doses: 1 mg, 10 mg, 25 mg. A total of 233 patients enrolled in the study and were randomized and blinded into three arms comprising 79 patients for each of the 25-mg and 1-mg doses, and 75 patients for the 10-mg dose. Patients were followed up for 12 weeks. The trial used the Montgomery-Åsberg depression rating scale (MADRS), a widely used and accepted scale for assessing depression; assessments were made by an independent, blinded rater. The primary endpoint was the change in the MADRS total score from baseline to week 3.

COMPASS Pathways plc  is a mental health care company dedicated to accelerating patient access to evidence-based innovation in mental health. Our focus is on improving the lives of those who are suffering with mental health challenges and who are not helped by current treatments. We are pioneering the development of a new model of psilocybin therapy, in which our proprietary formulation of synthetic psilocybin, COMP360, is administered in conjunction with psychological support. COMP360 has been designated a Breakthrough Therapy by the US FDA, for treatment-resistant depression (TRD), and we have completed a Phase 2b clinical trial of psilocybin therapy for TRD, in 22 sites across Europe and North America. This was the largest randomized, controlled, double-blind psilocybin therapy clinical trial ever conducted, and our topline data showed a statistically significant (p<0.001) and clinically relevant improvement in depressive symptom severity after three weeks for patients who received a single high dose of COMP360 psilocybin with psychological support. We are also running a Phase 2 clinical trial of COMP360 psilocybin therapy for post-traumatic stress disorder (PTSD). COMPASS is headquartered in London, UK, with offices in New York and San Francisco in the US. Our vision is a world of mental wellbeing. For more information, visit www.compasspathways.com.