Phase 2 Study of COMP360 Psilocybin Finds Improved PTSD Symptoms

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An international, multicenter phase 2 study (NCT05312151) of COMP360 psilocybin for posttraumatic stress disorder report met its primary safety and secondary efficacy endpoints.¹

The open label study included 22 patients with severe PTSD who received one 25 mg dose and psychological support. Average age at trial initiation was 35 years, and PTSD was a result of trauma experienced as an adult. Mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and Sheehan Disability Scale (SDS) total score at baseline was 47.5 and 22.7, respectively. Patients with complex PTSD as well as comorbid serious psychiatric disorders were excluded from the study.²

The study’s primary endpoint was safety of week 12, which was met. There were no treatment-emergent serious adverse events, and no patients withdrew from the study. The most common adverse event reported was headache (50%); nausea (36.4%), crying (27.3%), and fatigue (27.3%) were also reported. Suicide ideation (9%) was reported to be transient in 2 participants with a history of suicidality. The first event resolving on administration day, and the second event occurred in week 7 and resolved during the study.

The study’s secondary endpoints were changes in CAPS-5 and SDS total score from baseline and change in SDS total score from baseline, which was met. A 9.9 and 29.5 point reduction from CAPS-5 total score were observed at week 4 and 12, respectively. Similar results were observed on SDS total scores, which were 11.7 and 14.4 point reductions at week 4 and 12, respectively.

“Meaningful and sustained symptom improvement” was observed in terms of response and remission. At week 4, 81.8% of participants had experienced at least a 15 point improvement in their CAPS-5 score, which is was the defined response; response was 77.3% at week 12. Remission rates were similarly positive, with 63.6% meeting the remission definition of a score CAPS-5 score of 20 or less at week 4; at week 12, the response rate was 54.5%.

“There have been no new medicines approved for the treatment of PTSD in over 2 decades, and effective treatment options are limited,” principal investigator James Rucker, MD, PhD, said in a press statement.¹ Rucker is also Consultant Psychiatrist & Senior Clinical Lecturer and leads the Psychoactive Trials Group at the Centre for Affective Disorders at King’s College, London. “It’s promising to see positive signals from this study of investigational COMP360 psilocybin treatment in people with PTSD.”

“These promising results give us confidence to consider further robust evidence generation in the treatment of patients with PTSD,” Kabir Nath, CEO of Compass Pathways, told press.¹ “We are pleased to see the strong signal in PTSD, which, along with our prior data in treatment-resistant depression, lead us to believe that COMP360 has the potential to become an important treatment option for patients across a broad set of mental health conditions.”

Psilocybin have garnered considerable attention as a possible treatment agent for a number of psychiatric disorders, including PTSD, treatment resistant depression, and even eating disorders with psychological support. An investigational synthesized formulation of psilocybin, COMP360 was also found to be effective in improving depressive symptoms in a phase 2b study (p<0.001).

Compass is excited about the results from this study and what it might mean for patients with PTSD. “These observations, even with a small, open-label study, suggest that COMP360 could provide a clinically meaningful benefit and substantially improve patient daily function and quality of life,” Guy Goodwin, FMedSci, DPhil, chief medical officer of Compass Pathways and emeritus professor of psychiatry at The University of Oxford, said in a press statement.¹ “The well tolerated safety profile for COMP360 in patients with PTSD, with no serious adverse events observed, advance our understanding of potential applications of COMP360. We look forward to submitting the full results of this study for publication and potential presentation at an upcoming medical conference.”

References

1. Compass Pathways announces durable improvement in symptoms through 12 weeks in open-label phase 2 study of COMP360 psilocybin in post-traumatic stress disorder. Compass News. May 8, 2024. Accessed May 9, 2024. https://compasspathways.com/compass-pathways-announces-durable-improvement-in-symptoms-through-12-weeks-in-open-label-phase-2-study-of-comp360-psilocybin-in-post-traumatic-stress-disorder/

2. The Safety and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder.ClinicalTrials.gov identifier: NCT05312151. Updated April 9, 2024. Accessed May 9, 2024. https://clinicaltrials.gov/study/NCT05312151