FDA approves FILSPARI (sparsentan) to reduce proteinuria in adults and children aged ≥8 years with focal segmental glomerulosclerosis without nephrotic syndrome, supported by Phase 3 DUPLEX data showing significant reductions versus irbesartan.
Written By: Nikita Jha, Bpharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has approved FILSPARI (sparsentan) to reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome, marking the first approved treatment for this rare kidney disorder. The decision expands the reach of the therapy beyond IgA nephropathy into a second proteinuric kidney disease and introduces a targeted option for a population long managed with off-label therapies.
FSGS without nephrotic syndrome represents a clinically heterogeneous population aligned with KDIGO guidance for glomerular disease management. The company estimates that more than 30,000 individuals in the United States fall within this addressable group. Nephrotic syndrome is typically defined by proteinuria greater than 3.5 g/24 hours, edema, and serum albumin below 3.0 g/dL, criteria not present in this approved population.
Phase 3 DUPLEX Study Results
The approval is supported by findings from the Phase 3 DUPLEX study (NCT03493685), the largest head-to-head interventional trial conducted in FSGS. In the overall population, treatment with sparsentan produced a 46% reduction in proteinuria from baseline to Week 108 compared with 30% in patients receiving maximum labeled dose irbesartan (nominal p=0.0299).
Among patients without nephrotic syndrome, sparsentan demonstrated greater improvements, with a 48% reduction in proteinuria versus 27% with irbesartan (nominal p=0.0075). Patients treated with sparsentan also showed a modest benefit in kidney function decline, with a treatment difference of 1.1 mL/min/1.73 m² in eGFR change through Week 108. Across adult and pediatric populations, the therapy was generally well tolerated, with a safety profile comparable to irbesartan.
How Sparsentan Works
FSGS without nephrotic syndrome is largely driven by glomerular stress, inflammation, and scarring. Sparsentan targets both endothelin A and angiotensin II receptors, a dual pathway approach designed to reduce proteinuria and protect kidney function by limiting hemodynamic and inflammatory injury.
Expert and Company Perspectives
Eric Dube, president and chief executive officer of Travere Therapeutics, described the approval as a milestone for patients with FSGS and emphasized that the therapy expands the company’s rare kidney disease portfolio and will be immediately available for prescribing.
Kirk Campbell, president of the National Kidney Foundation, noted that treatment options for FSGS have historically relied on off-label approaches such as long-term steroid use. He highlighted that sparsentan delivered rapid and sustained proteinuria reductions in the DUPLEX study, particularly in patients without nephrotic syndrome, aligning with guideline recommendations that prioritize proteinuria reduction to slow disease progression.
Josh Tarnoff, chief executive officer of NephCure, characterized the approval as a long-awaited advancement for patients and families, reflecting collaboration among researchers, clinicians, and advocacy groups.
About FSGS
Focal segmental glomerulosclerosis is a rare kidney disorder characterized by progressive scarring of glomeruli and persistent proteinuria, which contributes to kidney damage and can lead to kidney failure. The disease affects both adults and children, and effective targeted therapies have historically been limited.
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