The phase 3 VISIONARY trial evaluated subcutaneous sibeprenlimab (400mg every 4 weeks) in adult patients with biopsy-confirmed immunoglobulin A (IgA) nephropathy, with complete 2-year estimated glomerular filtration rate (eGFR) slope results reported following earlier interim analyses.^1,2 Sibeprenlimab, a monoclonal antibody neutralizing a proliferation-inducing ligand (APRIL), demonstrated eGFR slope preservation over 104 weeks, accompanied by significant proteinuria reduction, suppression of pathogenic biomarkers, and resolution of microscopic hematuria with a safety profile comparable to placebo.^1-2

IgA nephropathy is the most common form of primary glomerulonephritis.⁴ Patients with this progressive disease face a highly significant lifetime risk of kidney failure.⁴ Approximately half of patients progress to kidney failure within 10-15 years of diagnosis, emphasizing that these patients remain at elevated risk unless their eGFR decline is maintained at ≤1ml/min/1.73m² per year.⁴ The Kidney Disease Improving Global Outcomes (KDIGO) guideline outlines the current standard of care, stressing the importance of comprehensive management, including the use of maximally tolerated renin-angiotensin system blockade and significant proteinuria reduction.⁵

Based on data from the phase 3 VISIONARY trial, the United States Food and Drug Administration (FDA) gave accelerated approval in November 2025 for sibeprenlimab to reduce proteinuria in adults with primary IgA nephropathy at risk of progression, dosed at 400mg every four weeks.⁶ VISIONARY is a multicenter, double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of subcutaneous sibeprenlimab.¹ Adult patients (n=510) with biopsy-confirmed IgA nephropathy receiving optimized supportive care were randomly assigned to receive either 400mg of sibeprenlimab or a matching placebo every four weeks for 100 weeks.¹

Topline 24-month eGFR slope results of the VISIONARY trial were presented at the Glomerular Disease Study & Trial Consortium (GlomCon) Europe 2026.² Sibeprenlimab demonstrated significant efficacy in stabilizing kidney function over 24 months, achieving an annualized eGFR slope treatment difference of +4.5mL/min/1.73m² per year (p<0.0001) compared to placebo.² The sibeprenlimab group maintained a stable annualized eGFR slope of +0.3mL/min/1.73m² per year, contrasting sharply with the placebo group's decline of 4.2mL/min/1.73m² per year.² A post hoc sensitivity analysis tracking the annualized slope directly from baseline confirmed these findings, revealing a +4.7mL/min/1.73m² per year difference.² By week 104, the least squares mean change in eGFR from baseline was +1.3mL/min/1.73m² for sibeprenlimab, compared to a substantial drop of 7.9mL/min/1.73m² for the placebo cohort.² These findings represent the largest eGFR effects reported to date in a phase 3 trial for IgA nephropathy, successfully meeting the 2025 KDIGO therapeutic target of limiting annual eGFR decline to less than 1mL/min/1.73m² per year.²

The safety profile of sibeprenlimab at 24 months remained favorable and highly comparable to the placebo.² Treatment-emergent adverse events (TEAEs) occurred at similar rates, affecting 90.7% of the sibeprenlimab cohort and 90.0% of the placebo cohort.² The sibeprenlimab group experienced fewer serious TEAEs (8.1% vs. 12.7%) and severe TEAEs (3.9% vs. 7.6%) than the placebo group.² While adverse events leading to treatment discontinuation were slightly higher for sibeprenlimab (4.0%) than placebo (1.2%), no deaths were reported in either group during the trial.² Localized injection-site reactions, including erythema, pain, and swelling, were also frequently reported across both study arms.²

A prespecified interim analysis at 9 months also evaluated key pharmacodynamic disease biomarkers.¹ Sibeprenlimab resulted in the rapid suppression of the targeted cytokine, with  APRIL reduced by 95.8% from baseline at week 48.¹ Consequently, serum levels of pathogenic galactose-deficient IgA1 decreased by 67.1% at week 48.¹ Complementing these findings, another interim analysis demonstrated that sibeprenlimab significantly impacts microscopic hematuria resolution, a key marker of active glomerular inflammation.³ 82.5% of sibeprenlimab-treated patients achieved microscopic hematuria resolution by week 48, compared to only 52.6% in the placebo group.³

In summary, 24-month results from the VISIONARY trial show that sibeprenlimab provides eGFR stabilization and proteinuria reduction in adults with progressive IgA nephropathy.² By meeting KDIGO annual eGFR slope targets with a safety profile comparable to placebo, these findings support APRIL inhibition as a therapeutic strategy for managing progressive disease.²