FDA Approval Targets Rare Kidney Disease

Phase 3 data showed greater proteinuria reduction vs irbesartan, with similar tolerability and a 1.1 mL/min/1.73 m² difference in estimated glomerular filtration rate at 108 weeks.

By
Kathryn Wighton
April 14, 2026
2 min

Conexiant

Overview

The FDA has approved FILSPARI (sparsentan) for reducing proteinuria in patients aged 8 and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. This marks the first pharmacologic treatment specifically approved for this rare kidney disease, based on positive results from the phase 3 DUPLEX trial.

Background

Focal segmental glomerulosclerosis is a rare kidney disorder characterized by progressive scarring of the glomeruli and proteinuria, which can lead to kidney failure. Prior to this approval, no pharmacologic treatments were specifically indicated for FSGS without nephrotic syndrome. Sparsentan, previously approved for immunoglobulin A nephropathy, targets endothelin A and angiotensin II receptors involved in kidney inflammation and scarring. The new indication potentially benefits an estimated 30,000 US patients with FSGS without nephrotic syndrome.

Data Highlights

Parameter	Sparsentan	Irbesartan
Proteinuria reduction at 108 weeks (all patients)	46%	30%
Proteinuria reduction at 108 weeks (without nephrotic syndrome)	48%	27%
Mean eGFR decline (mL/min/1.73 m²) at 108 weeks	−11.3	−12.4

Key Findings

FILSPARI (sparsentan) is the first FDA-approved pharmacologic treatment for FSGS without nephrotic syndrome in patients aged 8 years and older.
The phase 3 DUPLEX trial showed a 46% proteinuria reduction with sparsentan versus 30% with irbesartan at 108 weeks.
In patients without nephrotic syndrome, sparsentan reduced proteinuria by 48% compared to 27% with irbesartan.
Mean decline in estimated glomerular filtration rate was slightly less with sparsentan (−11.3 mL/min/1.73 m²) than irbesartan (−12.4 mL/min/1.73 m²).
Sparsentan targets endothelin A and angiotensin II receptors, addressing pathways involved in kidney inflammation and scarring.
Adverse effects include hypotension, hyperkalemia, peripheral edema, dizziness, and anemia; liver function monitoring is required due to hepatotoxicity risk.

Clinical Implications

Clinicians now have an FDA-approved option to reduce proteinuria in FSGS patients without nephrotic syndrome, potentially slowing disease progression. Monitoring liver function and avoiding use in pregnancy are essential due to safety concerns. Sparsentan’s dual receptor blockade offers a novel mechanism targeting kidney scarring pathways.

Conclusion

The FDA approval of sparsentan for FSGS without nephrotic syndrome represents a significant advancement in managing this rare kidney disease, providing a targeted therapy that reduces proteinuria and may preserve renal function.