The article Breaking News: Compass Pathways to run TWO Phase 3 Trials for Depression was originally published on Microdose.
Today, psychedelic medicine company Compass Pathways (Nasdaq: CMPS) announced a major update: rather than conducting just one Phase 3 clinical trial attempting to treat Treatment-Resistant Depression (TRD) with psilocybin-assisted therapy, the company will run two separate studies in tandem. Then, assuming positive results, Compass will work with the FDA to help legalize psilocybin for TRD treatment, perhaps as early as 2025.
These studies will be the two largest psychedelic medicine clinical trials ever conducted, with 378 and 568 patients respectively.
This news was delivered at the company’s Capital Markets Day, where the company’s leaders also walked through their Phase 2 programs using psilocybin therapy to treat PTSD and Anorexia Nervosa, as well as their therapist training program. They also discussed their commercialization and business strategy, though that is a topic for another article.
A look at Compass Pathways’ Phase 3 trials
The core difference between the two Phase 3 studies is the smaller one will test a single psilocybin dose of 25 mg against the placebo, while the larger will test two repeated doses, at either 25 mg or 10 mg.
Starting with the first Phase 3 clinical trial, named COMP 005, the first aspect to note is its size. With 378 participants in this “single dose monotherapy” trial, it is easily the largest ever psychedelic clinical trial — beating Compass’ previous Phase 2b trial with 233 patients. The trial will have a 2:1 randomization, meaning that 252 patients will receive the 25 mg dose of COMP360 — Compass’ proprietary crystalline psilocybin — paired with therapy, while the other 126 patients will receive a placebo and therapy. Of course, all patients will also undergo preparation therapy sessions before the 6-8 hour psychedelic session, as well as integration sessions after it. This will last 6 weeks in total.
The two core questions Compass hopes to answer in COMP 005 are:
- Can they replicate the treatment response seen in their Phase 2b trial?
- How does the safety profile of the treatment compare to the placebo?
The topline results of this trial are expected by the end of 2024.
The second Phase 3 clinical trial, named COMP 006, is simply massive. It will have 568 patients, easily beating out COMP 005 as the world’s largest-ever psychedelic clinical trial. As already stated, this trial will test two different dose levels of psilocybin, at 10 mg and 25 mg. Furthermore, each patient will receive two repeated doses (of the same strength) over the course of several weeks. Again, each patient will receive preparation and integration therapy sessions in addition to their psychedelic therapy session. This study will have a 2:1:1 randomization, meaning 284 patients will receive two doses of 25 mg, 142 will receive two doses of 10 mg, and 142 will receive the placebo (1 mg). This trial will also last 6 weeks.
The two core questions Compass hopes to answer in COMP 006 are:
- Can a second dose increase treatment responders and/or improve responses seen in their Phase 2b trial?
- Is there a meaningful treatment response to two doses of 10 mg?
The topline results of this trial are expected by mid-2025.
For both trials, the primary endpoint will be the reduction in depression symptoms as measured by the MADRS test. Throughout the trials, the main focus of Compass will be safety, efficacy, and quality.
The significance of Compass Pathways’ new Phase 3 setup
The decision to run two Phase 3 clinical trials in tandem is extremely significant. In order for a new medicine to be legalized, it must pass through at least two Phase 3 trials, with results being either more efficacious than current treatment methods, or safer. By running two trials simultaneously, Compass is betting that they can push psilocybin therapy for Treatment-Resistant Depression out of the research stage, and into clinics across America and eventually the world. They are of course working closely with the FDA at all steps to ensure that all procedures are being followed.
According to Trevor Mill, the Chief Development Officer, Compass is “confident that we will execute both pivotal studies, in parallel, and in the time we have forecasted.”
Treating Treatment-Resistant Depression is extremely important. By its very nature it is extremely difficult to treat, as someone who has TRD, by definition, has previously attempted treatment at least twice, to no avail. In other words, this is among the most difficult populations to treat.
According to Compass, 100 million people worldwide have depression that has so far been untreatable, and a person commits suicide every 40 seconds. That is the problem Compass is trying to solve.
And for many on the Compass team, this problem is personal. For example, co-founders Dr. Ekaterina Malievskaia and George Goldsmith’s son battled with depression, and CEO Kabir Nath’s father died of suicide.
As Goldsmith said during the presentation, “The fact that almost everyone has a story with mental health is why we founded Compass.”
Compass’ Phase 2b trial, while delivering positive results, was not as game-changing for TRD patients as some may have hoped. In that trial, of patients who received the 25 mg dose of psilocybin paired with therapy, three weeks after treatment 36.7% saw their depression symptoms (as measured by MADRS) decrease by 50% or more. However, by the time 12 weeks had passed, that number dropped to 24.1%.
This makes Compass’ COMP 006 more relevant, as we will get the chance to see whether a second dose of psilocybin can help sustain those results. Again, the TRD population is notoriously hard to treat, so even having a treatment that is effective for ⅓ of patients would be a major victory. Plus —and we would need Phase 3 data to back this up before declaring it definitely— it is likely that the treatment could be more effective in populations of people with less severe depression.
There is also the question of whether we will see many treatment-emergent adverse events, as in the 2b trial 83.5% of patients had adverse events, though only 6.3% of patients (5 people) had an “emergency” adverse event. Reducing this number is key to the ultimate success of psilocybin therapy for depression.psilocybin psychedelic therapy depression ptsd psilocybin-assisted therapy nasdaq capital compass fda research legalize legalized