Sibeprenlimab, which neutralizes A PRoliferation Inducing Ligand (APRIL), as a new approach to treating IgA nephropathy

INTRODUCTION: Immunoglobulin A (IgA) nephropathy is a common immune-mediated kidney disease leading to high blood pressure and may progress to kidney failure. None of the present treatments are disease-modifying or prolong life. The levels of A PRoliferation Inducing Ligand (APRIL) are raised in subjects with IgA nephropathy. Sibeprenlimab is a humanized IgG2 monoclonal antibody that binds to, and neutralizes, APRIL. AREAS COVERED: A phase 2 clinical trial of intravenous sibeprenlimab (VIS649) in IgA nephropathy: NCT04287985. The primary efficacy endpoint was the change from baseline in 24-h protein-to-creatinine ratio at 12 months, and this was reduced by sibeprenlimab. Sibeprenlimab also caused clinical remission in some subjects, stabilized estimated glomerular filtration rate (eGFR), and reduced galactose deficient IgA1, IgA, IgM, and IgG levels without causing any infections or other adverse events. EXPERT OPINION: Sibeprenlimab is a promising new approach to treating IgA nephropathy. The pharmaceutical company behind sibeprenlimab is also developing it for subcutaneous use, which would have advantages over intravenous use. As IgA nephropathy is a long-term progressive disease, key questions that need to be answered, over a long-time course, with sibeprenlimab are (i) whether its safety is maintained, and (ii) whether it improves clinical outcomes.