Crovalimab 340mg/2ml solution for injection vials

ABSTRACT Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life‐threatening disorder characterized by complement‐mediated hemolysis. Crovalimab, a novel anti‐C5 monoclonal antibody, may offer a more convenient alternative to current therapies, highlighting the need for a comprehensive analysis of its efficacy and safety. Methods A comprehensive search was conducted through PubMed, Embase, Cochrane, and clinicaltrials.gov using relevant keywords from inception until January 2025. Statistical calculation was conducted using MetaXL 5.3 by employing a random effects model to estimate the pooled event rates with 95% CI. Heterogeneity was assessed using the I2 and χ2 statistics. Results This meta‐analysis included four studies involving 275 patients with a mean age of 41.87 ± 13.34 years with rate of hemolysis control of 86% (95% CI: 77%–94%, I2 = 73%) and transfusion avoidance in 77% of patients (95% CI: 56%–93%, I2 = 90%), breakthrough hemolysis of 10% (95% CI: 6%–13%, I2 = 0%) and hemoglobin stabilization in 69% patients (95% CI: 43%–90%, I2 = 98%). The incidence rate of any adverse event was 89% (95% CI: 76%–98%, I2 = 87%) and serious adverse events 15% (95% CI: 7%–25%, I2 = 74%). Conclusion We observed high rates of hemolysis control and transfusion avoidance but significant adverse events. Study heterogeneity and publication bias limit generalizability, highlighting the need for larger, more robust trials. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission

Abstract licence: CC BY-NC-ND 4.0

AbstractCrovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low‐volume self‐administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open‐label, multicenter, phase 3 trial evaluating the non‐inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor‐naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co‐primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT‐Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non‐inferior to eculizumab in the co‐primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, −2.8 [−15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, −3.9 [−14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [−11.4, 16.3]). A clinically meaningful improvement in FACIT‐Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit–risk profile of crovalimab.

Abstract licence: CC BY 4.0