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sibeprenlimab   Click here for help

GtoPdb Ligand ID: 12102

Synonyms: sibeprenlimab-szsi | VIS-649 | VIS649 | Voyxact®
Approved drug Immunopharmacology Ligand
sibeprenlimab is an approved drug
Compound class: Antibody
Comment: Sibeprenlimab (VIS-649) is a fully humanized IgG2κ monoclonal antibody that targets the B-cell growth factor APRIL (TNFSF13) [3,6]. The antibody binds with high affinity to human trimeric APRIL, and potently blocks APRIL binding to its receptors TACI (transmembrane activator and CAML interactor) and BCMA (B-cell maturation antigen). APRIL mediates antibody class switching in mature B cells and promotes plasma-cell survival. APRIL acts to elevate production of IgA and pathogenic galactose-deficient IgA1, by mediating class switching in mature B cells and promoting plasma-cell survival. Galactose-deficient IgA1 is a key driver of the IgA nephropathy pathology. Hence targeting APRIL is considered as a mechanism to reduce IgA-mediated kidney damage.
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Summary of Clinical Use Click here for help
Sibeprenlimab was advanced to phase 3 clinical evaluations, to determine safety and efficacy as a mechanism to reduce pathological levels of circulating IgA in patients with IgA nephropathy [1]. First approval was granted by the FDA for this indication in November 2025 [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03719443 First in Human Study to Assess Safety of VIS649 in Healthy Subjects Phase 1 Interventional Visterra, Inc. Data from the first-in-human trial in healthy volunteers indicated that sibeprenlimab is safe and well tolerated. Target engagement was validated by reversible (and dose-dependent) suppression of APRIL levels, and reduction in circulating immunoglobulins (IgA, IgG, IgM). 5
NCT05248659 Phase 2/3 Open-Label Trial of Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy Phase 2/Phase 3 Interventional Otsuka Pharmaceutical Development & Commercialization, Inc.
NCT05248646 Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN) Phase 3 Interventional Otsuka Pharmaceutical Development & Commercialization, Inc. 7
NCT04287985 Safety and Efficacy Study of VIS649 for IgA Nephropathy Phase 2 Interventional Visterra, Inc. 4