Cybin Inc. has initiated its Phase 3 PARADIGM program to assess CYB003 for the adjunctive treatment of Major Depressive Disorder (MDD). The program comprises two 12-week randomized, placebo-controlled studies (APPROACH and EMBRACE) and a long-term extension study (EXTEND).
The first pivotal study, APPROACH, has already begun and will enroll 220 patients at 36 clinical sites across the U.S. and Europe. Topline results from APPROACH are expected in 2026. The second study, EMBRACE, is anticipated to begin in the first half of 2025. The EXTEND study, an open-label extension, will commence 12 weeks after the start of APPROACH and EMBRACE.
Phase 3 PARADIGM Program Details
The PARADIGM program is designed to evaluate the efficacy and safety of CYB003 in patients with moderate to severe MDD (MADRS ≥24) who are on a stable dose of antidepressant medication but are not responding adequately. The APPROACH trial will randomize participants 1:1 to receive either 16 mg of CYB003 or placebo, administered in two doses three weeks apart. The primary endpoint is the change in depressive symptoms, measured by the change in MADRS from baseline at six weeks after the first dose.
The EMBRACE trial will randomize 330 participants 1:1:1 to receive 16 mg of CYB003, 8 mg of CYB003, or placebo, also administered in two doses three weeks apart. The primary endpoint mirrors that of the APPROACH trial.
Participants from both APPROACH and EMBRACE will be eligible to enroll in the EXTEND study. During EXTEND, non-responders or those who relapse will be eligible to receive additional doses of CYB003.
Rationale and Design
According to Cybin CEO Doug Drysdale, the PARADIGM program incorporates protocols designed to address challenges encountered by peers by recruiting from the larger MDD population, administering CYB003 as an adjunctive treatment, and utilizing a 12-week blinded period. Amir Inamdar, Chief Medical Officer of Cybin, noted that the Phase 3 design was informed by Phase 2 data showing rapid and robust improvements in depression symptoms with a single dose of CYB003, and durable effects four months after two doses, with a 75% remission rate in the 16mg dose group.
Phase 2 Data Highlights
Phase 2 data demonstrated robust and sustained improvements in symptoms of depression with two doses of 12 mg or 16 mg of CYB003. The mean reduction from baseline in the MADRS total score was approximately 22 points in both dosing cohorts. Approximately 75% of patients were responders (≥50% improvement in MADRS scores) following two doses of 16mg, and 75% of patients on 16 mg were in remission from depression following 2 doses (MADRS score ≤10). CYB003 was well-tolerated, with no drug-related serious adverse events, and no incidents of suicidal ideation or behavior.
