Efficacy and safety of crovalimab versus eculizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria: Chinese subgroup analysis of the phase 3 COMMODORE 2 study.

内容摘要

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease with limited treatment options. The COMMODORE 2 study demonstrated that the novel C5 inhibitor crovalimab had comparable safety and non-inferior efficacy to eculizumab. We evaluated the safety and efficacy of crovalimab compared with eculizumab in the Chinese subpopulation of the global COMMODORE 2 study. Adult patients with PNH without previous complement inhibitor therapy were randomized (2:1) to crovalimab or eculizumab for 24 weeks. The co-primary endpoints were the proportions of patients achieving hemolysis control from Weeks 5-25 and those with transfusion avoidance from baseline to Week 25. The secondary endpoints included the proportion of patients with breakthrough hemolysis and hemoglobin stabilization from baseline to Week 25 and the mean change from baseline in FACIT-Fatigue score at Week 25. Safety data were assessed from baseline to the clinical cut-off (16 November 2022). The demographic and baseline characteristics of the 81 patients included (eculizumab: 27; crovalimab: 54) were well-balanced. In the crovalimab and eculizumab arms, respectively, hemolysis control was achieved in 88.3% and 86.8%, transfusion avoidance in 72.2% and 74.1%, hemoglobin stabilization in 72.2% and 70.4%, and breakthrough hemolysis in 5.6% and 11.1%. The FACIT-Fatigue score improvement was greater with crovalimab. Adverse events (81.5% vs. 88.9%) and grade 3-5 adverse events (24.1% vs. 33.3%) were less frequent with crovalimab. Over 24 weeks, 91% of patients achieved complete terminal complement inhibition with crovalimab. Crovalimab demonstrated at least comparable treatment performance and acceptable safety in Chinese patients with PNH.Clinical trial registrationClinicalTrials.gov identifier NCT04434092 (study registration was first posted on 16th June 2020).