Compass PathwaysAmong psychedelic companies, Compass Pathways plc (Nasdaq: CMPS) is noteworthy for having received Breakthrough Therapy designation from FDA for psilocybin in treatment-resistant depression in 2018. Now, Compass has completed the design of a Phase 3 pivotal study to test its COMP360 psilocybin therapy in treatment-resistant depression (TRD).

The Phase 3 study will be the first Phase 3 trial to investigate psilocybin internationally.

London-based Compass Pathways will divide its Phase 3 program into three clinical trials, which it anticipates will begin by the end of the year.

The first pivotal trial will test a 25-mg dose of psilocybin monotherapy against a placebo in approximately 378 volunteers.

The second study will administer a fixed repeat dose (1, 10 and 25 mg) in three dose arms. The trial aims to determine whether a repeat dose can improve recipients’ response.

Both pivotal studies will use change in MADRS score as the primary endpoint.

The final study will focus on long-term follow-up.

Dr. Guy Goodwin

Dr. Guy Goodwin

In Compass’s Phase 2b study, recipients of a 25 mg dose had a 6.6 MADRS reduction compared to those who received a 1 mg dose.

The company’s investigational TRD therapy comprises more than just administration of its crystalline proprietary psilocybin-based compound, said Dr. Guy Goodwin, the company’s chief medical officer. It includes “psychological support in an appropriate clinical setting and digital tools that include a therapist portal, an AI-driven analytics platform,” Goodwin said at an investor event.

“We expect patients to demonstrate reproducibility of response to the 25 mg dose [of psilocybin,” Goodwin said. “We envisage this may mean up to two to three doses per year, but it is unlikely to be a treatment that is necessarily suitable for everybody.”

The company believes its Phase 2b trial results demonstrated the potential for a rapid, sustained response in patients who failed to respond to two to four conventional antidepressant therapies.

CMPS shares fell 8.78% to $10.65 in early afternoon trading.

The company announced positive data from its Phase 2b program at the American Psychiatric Association annual meeting in May 2022. Depressed participants in that study who received a single 25 mg dose of psilocybin with psychological support had a statistically significant reduction in symptoms after three weeks based on the Montgomery-Åsberg Depression Rating Scale (MADRS).

In July, Compass named Big Pharma veteran Kabir Nath as its new CEO.