Urinary Biomarker Analysis Reveals Rapid Intrarenal Anti-inflammatory and Anti-fibrotic Effects of Sparsentan in IgA Nephropathy in the SPARTAN Study
Topics: Nephrology IgAN Sparsentan SPARTAN Clinical Poster Presentation Summary
Cheung CK, Barratt WA, Chaki S et al.
About the research
Summary
Background
- Sparsentan is a non-immunosuppressive, Dual Endothelin Angiotensin Receptor Antagonist (DEARA) indicated in the US to slow kidney function decline in adults with IgA nephropathy who are at risk for disease progression1-4
- In IgA nephropathy, sparsentan has demonstrated anti-inflammatory,* anti-proliferative,* anti-fibrotic,* and anti-proteinuric effects2,5-8
Aim
To examine the effects of sparsentan on the underlying pathophysiology of IgA nephropathy and report interim clinical findings for proteinuria and urinary biomarkers from SPARTAN
The Phase 2 SPARTAN open label, single-arm study was designed to assess the efficacy and safety of sparsentan as a first-line therapy in adult patients with IgA nephropathy (N=12)1
Figure. Study design1
About the figure
Changes in urinary biomarkers were measured by ELISA and normalized to creatinine concentration1
The SPARTAN study is being conducted at 5 participating sites in the UK1
Resources
Key findings
Baseline characteristics were previously described in an interim analysis of the SPARTAN trial9
Treatment with sparsentan in patients with IgA nephropathy led to rapid and sustained reductions in proteinuria, with urine protein‑creatinine ratio (UPCR) percentage decreasing by approximately 70% from baseline over 24 weeks1
Median UPCR decreased from 1.3 g/g (IQR: 0.4-1.7) at baseline to 0.3 g/g (IQR: 0.1-0.6) at Week 24 of sparsentan treatment1
Figure. Change in UPCR at each visit over 24 weeks1a
aOn-treatment analysis.
Treatment with sparsentan reduced urinary B-cell activating factor (BAFF) and soluble C5b9 (sC5b9), suggesting downregulation of B-cell and complement activation pathways1
Figure. Change in urinary BAFF and sC5b9 from baseline over 24 weeks1a
aOn-treatment analysis.
Decreases across inflammatory, profibrotic, chemokine, and cytokine urinary biomarkers were also seen in SPARTAN1
Dive deeper into the implications of urinary soluble CD163 (u-sCD163) levels, a biomarker for alternatively activated macrophages10
Clinical findings were consistent with preclinical data, as previous IgA nephropathy mouse models have demonstrated that treatment with sparsentan can attenuate gene expression specific to immune and inflammatory pathways including inflammatory pathway gene markers6,7
Figure. Change in urinary biomarkers from baseline over 24 weeks1a,b
aOn-treatment analysis.
bα2M, clusterin, and plasminogen analysis was performed only at baseline and Week 12.
Treatment with sparsentan was well tolerated with no new safety signals1
Conclusion
Interim findings from the SPARTAN trial show that treatment with sparsentan was well tolerated and leads to rapid and sustained reductions in proteinuria and urinary biomarkers of inflammation and fibrosis1
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Footnotes
*These effects are based on preclinical animal modeling data.
α2M, alpha-2-macroglobulin; BAFF, B-cell activating factor; CHI3L1, chitinase-3-like protein 1; CXCL10, C-X-C motif chemokine ligand 10; CXCL16, C-X-C motif chemokine ligand 16; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; ELISA, enzyme-linked immunosorbent assay; GDF15, growth/differentiation factor 15; IgA, immunoglobulin A; IL6, interleukin 6; IQR, interquartile range; MCP-1, monocyte chemoattractant protein-1; sCD163, soluble CD163; sC5b9, soluble C5b9; UPCR, urine protein-creatinine ratio.
- Cheung CK et al. Presented at: International Podocyte Conference & ISGD Meeting, 2025; June 10-13, 2025; Hamburg, Germany. FR_11.
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- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc. 9/2024.
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- Jenkinson C et al. Presentation at: International Symposium on IgA Nephropathy; September 27-29, 2018; Buenos Aires, Argentina.
- Cheung CK et al. Presented at: American Society of Nephrology, 2024; October 23-27, 2024; San Diego, USA. FR-OR63.
- Li J et al. Kidney International Reports. 2024;9(10):3016-3026.
MA-SP-25-0110 | August 2025