Work

A complement C5-targeted GalNAc-conjugated siRNA with sustained efficacy in a non-human primate model of IgA nephropathy

Year: 2026

Type: article

Abstract: value of 0.013 nM. In cynomolgus non-human primates, a single subcutaneous injection yielded sustained C5 suppression of over 80% for 2 months and more than 50% for up to 4 months, a duration significantly longer than is possible with existing complement inhibitors. Furthermore, we conducted a head-to-head efficacy comparison with Nefecon, an approved therapeutic agent for IgAN, in a cynomolgus monkey IgAN model. While both treatments showed comparable improvements in key renal function parameters, the C5-siRNA achieved superior pathological remission and near-complete blockade of glomerular C5 deposition and membrane attack complex formation. Collectively, this study provides a strong rationale for the clinical development of C5-siRNA as an excellent therapy for IgAN, either as a standalone monotherapy or in combination with agents targeting upstream pathogenic pathways.

Source: Molecular Therapy

DOI: 10.1016/j.ymthe.2026.08.022