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

Abstract 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 one or more narsoplimab courses at 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 enrolled in substudy 1 had reductions in 24-hr 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-hr UPE in these 8 patients was 61.4% at 31–54 weeks post-baseline. The eGFR remained stable in both substudies. Conclusion This interim analysis suggests that narsoplimab treatment is safe, well-tolerated, and may result in clinically meaningful reductions in proteinuria and stability of eGFR in high-risk patients with advanced IgAN.