COMPASS Pathways’ (NASDAQ:CMPS) Phase 2b study of synthetic psilocybin COMP360 paired with psychological support for Treatment-Resistant Depression (TRD) is still nourishing the psychedelics research field, as newly published data demonstrate the therapy’s potential beyond the reduction of depression.
These outcomes point to greater improvement in anxiety, quality of life, positive and negative emotions, cognitive function and ability to take part in everyday tasks as reported by participants who received 25mg psilocybin single doses vs. those who received the 1mg single doses after three weeks. The 10 mg group also self-reported improvements as compared with the 1 mg group, although to a lower degree.
The 25 mg dose was associated with an increase in the positive affect score and a decrease in the negative affect score at Week 3 after dosing.
The anxiety measure also showed that the 25 mg dose produced greater improvement compared with the 1 mg dose than the 10 mg dose at Week 3.
The 25 mg and 10 mg doses also improved measures of function at Week 3.
Effects on quality of life and cognitive function were smaller at Week 3.
At Week 12, the treatment differences were less pronounced, however maintaining the same dose-dependent trends.
Quick Q&A With COMPASS
The study’s findings seem to make the case for psilocybin’s multifaceted effect on a set of measures related to TRD, further supporting its development in treating this disease.
Although COMPASS admits further trials should be done to test whether results are replicated, the current ones represent the largest dataset so far from a randomized, controlled clinical trial of a serotonergic agonist producing a psychedelic experience.
The company’s CMO, Dr. Guy Goodwin explained the importance of the positive results that show promise that challenge a difficult condition such as TRD.
“These are people who have tried at least two treatments for their depression without success and chances of response decrease with every subsequent treatment. Our Phase 2b study showed that, after a single 25mg dose of COMP360 psilocybin therapy, approx. 30% of patients with TRD were in remission at week three as measured via the MADRS depression scale, a widely used clinicianâ€rated measure of depressive severity.”
The additional data recently published adds the patients’ perspective of the psilocybin experience.
“We asked patients to report on changes in their depression, anxiety, the extent to which they could return to work, their mood and quality of life and many reported meaningful changes. This is significant for this patient population who have not responded to the current standard of care,” Goodwin told Benzinga.
Also, following the 12-week post-administration period, a long-term follow-up study was available to some Phase 2 study participants. And findings were supportive of the Phase 3 program design (editor’s note: this latter design has recently been modified towards a reduction in sample size in one of the two studies, as reported by Psychedelic Alpha.)
As Goodwin stated, COMPASS expects to evaluate the qualitative experience and its relationship to long-term outcomes “more thoroughly” in the Phase 3 program, where “the necessary follow-up will be more comprehensive than was possible in our Phase 2 study” and, also, the value of multiple doses will be assessed.
The upcoming Phase 3 trials will aim to include greater diversity. In that clinical trials “demand a lot from the participants, they tend to favor the recruitment of patient populations with more resources.”
For this one, clinical trial sites were selected to include locations with a higher proportion of racial and ethnic minority patients. The company “will work closely with the sites in tailored community engagement, to encourage broader ethnic and socio-economic diversity in recruitment,” Goodwin said.
As for how to read the serious adverse events (although present in few cases proportionately) in the Phase 2b trial, Goodwin said participants were at high risk of suicidality. After having tried multiple treatments for their depression without success, there was no mean worsening of suicidal ideation scores in any treatment group and no suicides or attempted suicides.
“However, we used a sensitive scale that detected some uptick from low levels in all treatment groups. It was slightly more likely in the groups treated with 10mg and 25mg and suicidal behaviors were reported in three non-responders in the 25mg arm one month or more after COMP360 administration,” he explained.
Emergent suicidality could be more closely related to the course of depressive illness in the TRD population than the drug treatment per se, Dr. Goodwin pointed out. “The risk of suicide in the patient population underlines the importance of our approach to regulatory approval through a proper drug development program for which a large-scale Phase 3 program is crucial.”