The US Food and Drug Administration approved FILSPARI (sparsentan) to reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis without nephrotic syndrome, marking the first approved pharmacologic treatment for this condition.
Focal segmental glomerulosclerosis is a rare kidney disorder characterized by progressive glomerular scarring and proteinuria, which contributes to ongoing renal injury and may lead to kidney failure. The newly approved indication expands sparsentan’s use beyond immunoglobulin A nephropathy. It applies to an estimated 30,000 patients in the US without nephrotic syndrome, with a broader potential population exceeding 100,000 when including both indications.
The approval was supported by data from the phase 3 DUPLEX trial, a randomized, double-blind, active-controlled study that enrolled 371 patients aged 8 to 75 years with biopsy-proven or genetic focal segmental glomerulosclerosis. At 108 weeks, patients treated with sparsentan demonstrated a 46% reduction in proteinuria from baseline compared with 30% among those receiving irbesartan. In the subgroup without nephrotic syndrome, proteinuria reductions were 48% with sparsentan vs 27% with irbesartan.
Mean estimated glomerular filtration rate decline from baseline to week 108 was −11.3 mL/min/1.73 m² with sparsentan vs −12.4 mL/min/1.73 m² with irbesartan. Sparsentan targets endothelin A and angiotensin II receptors, pathways associated with inflammation and scarring in the kidney.
Sparsentan demonstrated similar tolerability to irbesartan in both adult and pediatric patients. Frequently reported adverse effects included hypotension, hyperkalemia, peripheral edema, dizziness, and anemia.
Sparsentan is available through a restricted risk evaluation and mitigation strategy program because of hepatotoxicity risk. Liver function should be assessed before treatment initiation and monitored during therapy. The drug is contraindicated in pregnancy because of embryo-fetal toxicity.
Source: Travere Therapeutics