Treatment with the psychedelic drug psilocybin (COMP360) was associated with a significant reduction in depressive symptom severity in patients with treatment-resistant depression, according to results from a phase 2b trial.
The controlled, double-blind trial (ClinicalTrial.gov Identifier: NCT03775200) enrolled 233 patients, making it the largest psilocybin trial to date. Participants discontinued antidepressants prior to trial initiation, then were randomly assigned to receive a single dose of either 25mg (n=79), 10mg (n=75), or 1mg (n=79) of psilocybin. The primary endpoint of the study was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score.
Results showed that the difference in MADRS total scores at week 3 between the 25mg group and the 1mg was -6.6 points (P <.001); a statistically significant difference was observed between day 2 up to week 6.
At week 3, 36.7% (n=29) of patients in the 25mg group showed response vs 17.7% (n=14) of patients in the 1mg group. Remission at week 3 was achieved by 29.1% (n=23) of patients in the 25mg group and 7.6% (n=6) of patients in the 1mg group. Sustained response at week 12 was observed in 24.1% (n=19) patients in the 25mg group and 10.1% (n=8) of patients in the 1mg group.
When the 10mg dose was compared with the 1mg dose, a statistically significant difference was not observed at week 3 (numerical treatment difference: -2.5 points; P =.184).
As for adverse events, 179 patients reported at least 1. Twelve patients reported serious adverse events, including suicidal behavior, intentional self-injury and suicidal ideation. These occurred more frequently in the 25mg group than the 10- or 1mg groups.
George Goldsmith, CEO and co-founder of Compass Pathways said, “With these compelling data, we will urgently progress our clinical development program and move closer to making this therapy accessible to patients in need, if approved.”
In October 2018, the Food and Drug Administration (FDA) granted Breakthrough Therapy designation to psilocybin for the treatment of major depressive disorder. Breakthrough designation allows for an accelerated pathway to approval.
Currently, psilocybin, a serotonin receptor agonist, is classified as a Schedule I drug in the US as it has not been approved by the FDA for any therapeutic use.
COMPASS Pathways announces positive topline results from groundbreaking phase IIb trial of investigational COMP360 psilocybin therapy for treatment-resistant depression. News Release. COMPASS Pathways. Accessed November 11, 2021. https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-positive-topline-results.