Safety, Tolerability and Efficacy of Narsoplimab, a Novel MASP-2 Inhibitor for the Treatment of IgA Nephropathy

Introduction Narsoplimab is a human monoclonal antibody against mannan-associated lectin-binding serine protease−2 (MASP-2). Now in a phase 3 study, narsoplimab was evaluated in a staged phase 2 study assessing safety and effectiveness in high-risk patients with IgA nephropathy (IgAN). Methods Substudy 1 was a single-arm open-label study of 12 weekly infusions and tapered corticosteroids, with 6 weeks of follow-up. In substudy 2, patients were randomized 1:1 to receive a course of treatment consisting of once-weekly narsoplimab or vehicle infusions for 12 weeks. After 6 weeks of follow-up, both substudy 2 groups could continue in an open-label extension, receiving 1 or more narsoplimab courses at the investigator’s discretion. Results The most commonly reported adverse events (AEs) included headache, upper respiratory infection, and fatigue. Most AEs were mild or moderate and transient. No treatment-related serious AEs were reported. All 4 patients who were enrolled in substudy 1 had reductions in 24-hour urine protein excretion (UPE) at week 18, ranging from 54% to 95% compared with baseline. In substudy 2, the vehicle and narsoplimab groups had similar proteinuria reductions at week 18. Eight patients (3 vehicle, 5 narsoplimab) continued in the dosing extension; all received narsoplimab. Median reduction in 24-hour UPE in these 8 patients was 61.4% at 31 to 54 weeks postbaseline. Estimated glomerular filtration rates (eGFR) remained stable in both substudies. Conclusion This interim analysis suggests that narsoplimab treatment is safe, is well tolerated, and may result in clinically meaningful reductions in proteinuria and stability of eGFR in high-risk patients with advanced IgAN.