Sparsentan's Effect on Urinary Biomarkers in IgAN, With Chee Kay Cheung, MBChB, PhD

New data from the ongoing SPARTAN study highlight the potent antiproteinuric and immunomodulatory effects of sparsentan (Filspari), a dual endothelin and angiotensin receptor antagonist, in adults with newly diagnosed IgA nephropathy (IgAN).

Interim 24-week findings, presented at American Society of Nephrology (ASN) Kidney Week 2025 by investigators from the SPARTAN trial, reveal substantial reductions in proteinuria and multiple urinary biomarkers of inflammation and fibrosis, regardless of baseline proteinuria levels.

Sparsentan received its first approval from the US Food and Drug Administration (FDA) in the form of an accelerated approval for reducing proteinuria in patients with IgAN in 2023 based on the phase 3 PROTECT trial. The FDA granted full approval granted full approval for slowing kidney function decline in adults with primary IgAN who are at risk of disease progression in September 2024. In August 2025, the FDA approved an update to the REMS program for sparsentan to reduce the frequency of liver function monitoring to every 3 months from the onset of treatment and remove the embryo-fetal toxicity monitoring requirement.

The analysis at Kidney Week 2025 included 12 adults with biopsy-proven IgAN within 6 months of diagnosis, proteinuria ≥0.5 g/day, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², and no prior ACE inhibitor or ARB therapy. Participants received sparsentan for up to 110 weeks. One patient discontinued due to hypotension, leaving 11 evaluable participants for this interim analysis. Biomarkers were measured by ELISA at baseline, weeks 6, 12, and 24, normalized to creatinine concentration, and analyzed by baseline proteinuria strata: <1 g/day (n=5) and ≥1 g/day (n=6).

Baseline characteristics were similar between groups, although those with high proteinuria (≥1 g/day) had lower mean eGFR (53 vs 92 mL/min/1.73 m²) and greater median proteinuria (3.3 vs 0.6 g/day). Baseline biomarker concentrations were 2- to 10-fold greater in the high proteinuria cohort, with the greatest elevations seen in GDF15, MCP1, CXCL16, BAFF, sCD163, C5b9, and IL6.

At week 24, proteinuria decreased by 80% from baseline in the high proteinuria group compared to 48% in the low proteinuria group. Across all participants, urinary biomarker levels declined by 16% to 76%. Reductions were similar between strata except for IL6 and C5b9, where decreases were more pronounced among high proteinuria patients. Notably, C5b9 levels fell by 84% in the high proteinuria group versus 35% in the low proteinuria group, normalizing to comparable absolute levels between groups.

Investigators concluded that sparsentan achieved rapid and sustained antiproteinuric effects and was associated with consistent reductions in inflammatory, profibrotic, and complement activation markers, suggesting mechanistic benefits extending beyond hemodynamic modulation.

Relevant disclosures for Cheung include Travere Therapeutics, Alexion, Alpine Immune Sciences, Calliditas Therapeutics, CSL Vifor, Novartis, Otsuka Pharmaceutical, Roche, Vera Therapeutics, and others.

References:

1. Cheung CK, Barratt WA, Dhaun N, et al. Effect of Sparsentan (SPAR) on Proteinuria and Urinary Inflammatory and Profibrotic Biomarkers by Baseline Proteinuria Strata in SPARTAN Study Participants with IgAN. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

2. Travere Therapeutics. Travere Therapeutics Announces U.S. FDA Approves REMS Modification for FILSPARI® (sparsentan) in IgA Nephropathy. Travere.com. Published August 27, 2025. Accessed November 7, 2025. https://ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-Announces-U-S--FDA-Approves-REMS-Modification-for-FILSPARI-sparsentan-in-IgA-Nephropathy/default.aspx