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 IgA nephropathy (IgAN).

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.1

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.2

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.1

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 24.1

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.1

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.1

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, Dhaun N, Griffin SV, et al. 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.

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