Chee Kay Cheung MBChB PhD, is a consultant nephrologist and honorary senior lecturer at the University of Leicester.

Chee Kay Cheung, MBChB, PhD

PROTECT: Sparsentan Offers CV Protection Benefits as First-Line Therapy in IgAN

An interim analysis from the SPARTAN study offers new insight into the cardiovascular safety profile of sparsentan (Filspari), a dual endothelin and angiotensin receptor antagonist, used as first-line therapy in adults with 

Findings from the 24-week analysis, which were presented at the 

American Society of Nephrology (ASN) Kidney Week 2025

, suggest sparsentan produces rapid reductions in proteinuria alongside favorable trends in blood pressure, cardiac structure, and cardiovascular biomarkers.

Sparsentan received accelerated approval from the US Food and Drug Administration (FDA) 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 and, in August 2025, 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 SPARTAN study is an ongoing, open-label, single-arm exploratory trial designed to evaluate the safety and efficacy of sparsentan over 110 weeks in adults with biopsy-confirmed IgAN. Eligible participants were required to have proteinuria ≥0.5 g/day, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², and no prior ACE inhibitor or ARB therapy. Twelve adults were enrolled, 1 of whom discontinued early due to hypotension, leaving 11 evaluable participants for this interim analysis.

At baseline, participants had a mean age of 35.8 years (SD, 12.2), median proteinuria of 1.7 g/day (IQR, 0.6 to 3.3), and mean eGFR of 70.2 mL/min/1.73 m² (SD, 25.0). Sparsentan treatment resulted in rapid and sustained proteinuria reductions of approximately 70% over 24 weeks. Blood pressure declined initially and remained stable, with mean changes of –15/–8 mmHg at week 24.

Additional analyses demonstrated improvements in cardiovascular parameters. Mean body weight decreased by 1.0 kg (SD 3.3) and total body water by 4.4 L (SD, 14.8). NT-proBNP levels declined by a mean of –11.2 ng/mL (SD, 52.0), suggesting no signal for cardiac stress or fluid overload.

Paired cardiac MRI scans from 8 participants showed evidence of early reverse cardiac remodeling, with a mean reduction in left ventricular (LV) mass of –3.1 g/m² (SD, 3.5) by week 24. LV ejection fraction remained stable (+0.3%, SD 6.6), while stroke volume modestly increased (+2.1 mL; SD, 5.6). Changes in native T1 (+12.9 ms; SD, 35.1) and T2 (+2.3 ms; SD, 3.8) times were mild, and right ventricular parameters were unchanged.

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

Evaluation of Cardiovascular Risk Factors, Structure, and Function in an Interim Analysis of the SPARTAN Study: Sparsentan as First-Line Treatment of Incident Patients with IgAN. 

Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

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

Videos

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

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

 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.

Effect of Sparsentan (SPAR) on Proteinuria and Urinary Inflammatory and Profibrotic Biomarkers by Baseline Proteinuria Strata in SPARTAN Study Participants with IgAN. 

Cheung explores the effect of sparsentan on urinary biomarkers in treatment-naive patients with IgA nephropathy.

Chee Kay Cheung, MBChB, PhD

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