Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor‐naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single‐arm study

Abstract The Phase 3 single‐arm COMMODORE 3 study ( ClinicalTrials.gov , NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor‐naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor‐naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every‐4‐weeks subcutaneous maintenance doses per weight‐based tiered‐dosing schedule. Co‐primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15–58 years old) were enrolled; all received treatment. At primary analysis, both co‐primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8–86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant ( p < .0001). No adverse events led to treatment discontinuation. One treatment‐unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every‐4‐weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor‐naive patients with PNH.