Travere Therapeutics announced that the US FDA has granted full approval to Filspari (sparsentan) to reduce proteinuria in adults and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. The approval makes Filspari the first and only medicine approved by the US FDA specifically for FSGS, extending the drug’s reach beyond its existing indication in IgA nephropathy (IgAN) into a second rare kidney disease.
The approved indication covers patients with FSGS who do not meet the concurrent criteria for nephrotic syndrome, defined as proteinuria greater than 3.5 g/24h, edema, and serum albumin below 3.0 g/dL. Travere estimates this population at more than 30,000 individuals in the US. The label aligns with Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for managing glomerular diseases, which emphasize proteinuria reduction as a primary strategy to slow disease progression. Combined with the existing IgAN indication, the company said the total addressable US population now exceeds 100,000 patients. Filspari is available only through the FILSPARI Risk Evaluation and Mitigation Strategy (REMS) program due to hepatotoxicity risk, requiring enrolment of prescribers, patients, and pharmacies, with mandatory liver function monitoring every three months.
The approval was supported by the Phase III DUPLEX study, described by Travere as the largest head-to-head interventional trial conducted in FSGS to date. The global, randomized, double-blind, active-controlled trial enrolled 371 patients aged 8 to 75 years with biopsy-proven or genetic FSGS, randomized 1:1 to sparsentan titrated to 800 mg or irbesartan titrated to 300 mg. The prespecified confirmatory primary endpoint was rate of change in eGFR from baseline to Week 108; this endpoint did not reach statistical significance for superiority over irbesartan. However, in the overall study population, sparsentan produced a 46% reduction in proteinuria from baseline to Week 108 compared with 30% for irbesartan. In the subgroup without nephrotic syndrome, the proteinuria reduction was 48% versus 27% for irbesartan, a difference that was statistically significant (nominal p-value 0.0075). Patients without nephrotic syndrome treated with sparsentan also showed a mean eGFR change of -11.3 mL/min/1.73 m² compared with -12.4 mL/min/1.73 m² for irbesartan, a treatment difference of 1.1 mL/min/1.73 m². The safety profile was described as generally comparable to irbesartan across both adult and pediatric patients. The most common adverse reactions occurring in 5% or more of FSGS patients receiving Filspari were peripheral edema, hypotension, hyperkalemia, dizziness, and anemia. The two-year results were published in the New England Journal of Medicine.
FSGS is a rare progressive kidney disorder characterized by scarring of the glomeruli, with protein leakage into the urine considered directly toxic to renal tubules and a driver of further disease progression toward end-stage kidney disease. Prior to this approval, no medicine had received US FDA authorization specifically for FSGS, and clinical management relied on off-label use of corticosteroids, calcineurin inhibitors such as cyclosporine and tacrolimus, and renin-angiotensin system blockers including angiotensin receptor blockers. Sparsentan’s dual mechanism targets both endothelin A and angiotensin II receptors, addressing pathways associated with glomerular stress, inflammation, and scarring.
For Travere, the FSGS approval adds a second approved indication to a drug already positioned as the most commonly prescribed US FDA-approved medicine for IgAN, and extends the company’s presence in rare kidney disease. The approval also marks a notable regulatory outcome for a disease area that had, until now, lacked any approved therapy, despite the progressive nature of FSGS and its potential to culminate in dialysis or transplantation.