Efficacy and safety of sibeprenlimab in IgA nephropathy: interim analysis of the China cohort in the phase 3 VISIONARY trial.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is a progressive immune-mediated chronic kidney disease with a high prevalence and disease burden in East Asia, including China. In a prespecified interim analysis (IA) of the global phase 3 VISIONARY trial, treatment with sibeprenlimab led to significant placebo-adjusted reduction in 24-hour urine protein-to-creatinine ratio (uPCR-24h) of 51.2% (P < .0001) at 9 months. Here, we report the interim efficacy and safety findings for sibeprenlimab for patients with IgA nephropathy enrolled from mainland China as part of the main global population. METHODS: Patients (N = 102) were randomized 1:1 to receive sibeprenlimab 400 mg or placebo subcutaneously Q4W for 26 doses. Patients who completed the 9-month uPCR-24h assessment were included. The primary endpoint was change in uPCR-24h from baseline at 9 months. The key secondary endpoint of annualized estimated glomerular filtration rate slope over 24 months will be reported at trial completion. Other secondary and exploratory endpoints included spot urine protein-to-creatinine ratio (spot uPCR), proteinuria remission, haematuria resolution, reduction in biomarker levels [including galactose-deficient IgA1 (Gd-IgA1) and a proliferation-inducing ligand (APRIL)], and safety. RESULTS: By the China IA data cutoff (January 2025), 42 patients from mainland China completed the 9-month uPCR-24h assessment (sibeprenlimab, n = 25; placebo, n = 17) and were included in the efficacy analysis. At 9 months, a reduction from baseline in uPCR-24h of 63.1% was observed in sibeprenlimab-treated patients versus a decrease of 3.1% in the placebo group, corresponding to a placebo-adjusted reduction of 61.9% (95% confidence interval 43.2%-74.5%). Spot uPCR declined by week 4 and was sustained through month 12. Sibeprenlimab reduced Gd-IgA1 (67.3%) and suppressed APRIL levels (97.7%) from baseline at week 48. The incidence of treatment-emergent adverse events was similar between treatment groups. CONCLUSIONS: Interim efficacy and safety results for the mainland China cohort were consistent with the IA of the global cohort of the VISIONARY trial (ClinicalTrials.gov: NCT05248646).