Abstract: FR-PO0809
Effect of Sparsentan (SPAR) on Proteinuria and Urinary Inflammatory and Profibrotic Biomarkers by Baseline Proteinuria Strata in SPARTAN Study Participants with IgAN
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cheung, Chee Kay, Leicester General Hospital, Leicester, England, United Kingdom
- Barratt, William Alfred, University of Leicester, Leicester, England, United Kingdom
- Dhaun, Neeraj, Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
- Griffin, Sian V., Department of Nephrology and Transplantation, University Hospital of Wales, Cardiff, United Kingdom
- Hendry, Bruce M., Travere Therapeutics, Inc., San Diego, California, United States
- Jama, Amal A A, University of Leicester, Leicester, England, United Kingdom
- Khan, Ishika, University of Leicester, Leicester, England, United Kingdom
- Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States
- Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
- Moody, Stephanie, Travere Therapeutics, Inc., San Diego, California, United States
- Nawaz, Nadia, University of Leicester, Leicester, England, United Kingdom
- Sayer, Matthew, Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
- Sinha, Smeeta, Department of Renal Medicine Salford Royal Hospital Northern Care Alliance NHS FoundationTrust, Salford, United Kingdom
- Willcocks, Lisa, Department of Renal Medicine, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom
- Barratt, Jonathan, Leicester General Hospital, Leicester, England, United Kingdom
Background
Interim analysis of SPARTAN showed treatment with SPAR, a dual endothelin and angiotensin receptor antagonist, results in rapid and sustained proteinuria (PU) reductions of ~70% over 24 wks in incident pts with IgAN. Here we present findings on changes in PU and biomarkers of inflammation, fibrosis and B-cell and complement activation, stratified by baseline (BL) PU (<1 g/d and ≥1 g/d).
Methods
12 adults with biopsy-proven IgAN within 6 mo, PU ≥0.5 g/day, eGFR ≥30 mL/min/1.73 m2, and no prior ACEi/ARB treatment were enrolled. SPAR treatment is for 110 wks. One pt discontinued early due to hypotension. Changes in urinary biomarkers measured by ELISA, normalized to creatinine concentration, were analysed in the remaining 11 pts at BL, 6, 12 and 24 wks.
Results
There were no marked differences in demographics between <1 (n=5) and ≥1 g/d (n=6) strata, however, in the high PU group BL eGFR was notably lower (mean: 53 vs 92 mL/min/1.73 m2), while PU was greater (median: 3.3 vs 0.6 g/d), as were biomarker levels (2 to 10-fold; increasing order of magnitude GDF15, MCP1, CXCL16, BAFF, sCD163, C5b9, IL6). PU reduction from BL at wk 24 was greater for the ≥1 g/d group (80% vs 48%). All biomarker levels were lower by wk 24 (16 to 76%), with comparable reductions between strata for all but IL6 and C5b9, where observed changes were more pronounced in the ≥1 g/d group. For C5b9, the reduction in the high PU group (84% vs 35%) brought C5b9 to absolute levels comparable to the low PU group.
Conclusion
SPAR is a very potent antiproteinuric medication in incident patients with IgAN, particularly for those with high PU (80% reduction at wk 24) and elevated levels of biomarkers that promote inflammation, fibrosis, and B cell and complement activation. Responses to SPAR as first-line therapy occurred rapidly and were sustained in at risk participants with lower or higher-grade PU. These data enhance the scope of SPAR mode of action to cellular effects well beyond haemodynamic actions, limiting the consequences of IgA deposition within the glomerulus and tubule.
Funding
- Commercial Support – Travere Therapeutics, Inc.