Sparsentan as First-Line Treatment in IgAN From SPARTAN

The PROTECT trial demonstrated that sparsentan reduces proteinuria and preserves kidney function in patients with IgA nephropathy (IgAN). However, its potential as first-line therapy requires further investigation. SPARTAN (NCT04663204) is an experimental study evaluating efficacy, safety, and mechanistic actions of sparsentan in incident patients with IgAN. We present findings from a prespecified 24-week interim analysis.

A total of 12 adults with incident biopsy-proven IgAN, urine protein excretion (UPE) ≥ 0.5 g/d, estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m², and no renin-angiotensin system inhibitor (RASi) treatment within the previous 12 months were enrolled. Sparsentan was administered for 110 weeks with a 4-week safety follow-up. Assessments included proteinuria, eGFR, blood pressure (BP), body weight, total body water, cardiovascular measures, urinary biomarkers, and safety.

Mean age was 35.8 years, median (interquartile range [IQR]) UPE was 1.7 (0.6-3.3) g/d, and mean eGFR was 70.2 (SD: 25.0) ml/min per 1.73 m² at baseline. Urine protein-to-creatinine ratio (UPCR) declined rapidly (-61.9% at week 4), and reductions were sustained over 24 weeks (-68.8%); 58% of patients achieved complete remission of proteinuria (<0.3 g/d) during treatment. After an initial decrease, BP remained stable with stable eGFR, body weight, and cardiovascular risk variables. Total body water decreased. Rapid and sustained reductions in urinary biomarkers of inflammation, immune cell recruitment and modulation, and fibrosis were observed. The most frequent adverse event was dizziness (50% patients); 1 patient discontinued because of hypotension.

First-line sparsentan reduced proteinuria by approximately 70% over 24 weeks and was generally well tolerated. Biomarker observations support anti-inflammatory and antifibrotic effects of sparsentan beyond its hemodynamic effects.