Understanding Sparsentan in Pediatric FSGS, With Michelle Rheault, MD

New data from a subgroup analysis of the phase 3 DUPLEX trial demonstrate that sparsentan (Filspari), a non-immunosuppressive dual endothelin and angiotensin receptor antagonist, achieves rapid, sustained, and superior reductions in proteinuria compared with irbesartan in pediatric patients with focal segmental glomerulosclerosis (FSGS).

These data come at a pivotal time, as a January 2026 PDUFA date could result in sparsentan becoming the first agent to receive an indication for FSGS. The agent already boasts approval for use in IgA nephropathy dating back to 2023.

The parent DUPLEX trial, a 108-week, randomized, active-controlled study, included 371 participants with biopsy-confirmed FSGS. Participants were randomized to receive sparsentan 800 mg/day (>50 kg) or 400 mg/day (≤50 kg), versus irbesartan 300 mg/day (>50 kg) or 150 mg/day (≤50 kg). Key outcomes included change in urine protein-to-creatinine ratio (UPCR), complete remission (CR), FSGS partial remission endpoint (FPRE), and a composite kidney endpoint of ≥40% eGFR decline, kidney failure, or death.

Presented at the American Society of Nephrology (ASN) Kidney Week 2025, this pediatric subgroup analysis included 35 patients under 18 years of age, with 16 treated with sparsentan (median age, 14.5 years) and 19 with irbesartan (median age, 14.0 years). Baseline demographic and clinical characteristics were comparable between groups.

By week 108, sparsentan led to a mean 39.5% reduction in UPCR, compared with 24.9% with irbesartan, reflecting greater and more durable antiproteinuric efficacy. Complete remission of proteinuria (UPCR <0.3 g/g) was achieved by 12.5% of SPAR-treated patients versus 5.3% with IRB, while FPRE (UPCR ≤1.5 g/g and >40% reduction) was observed in 56.3% vs 36.8%, respectively. Additionally, fewer pediatric patients receiving sparsentan progressed to the composite kidney endpoint compared with irbesartan, consistent with the renal protective trends seen in the overall DUPLEX population.

Sparsentan demonstrated a favorable safety profile comparable to irbesartan. No patients in the sparsentan arm discontinued therapy due to adverse events, compared with 2 patients (10.5%) in the irbesartan group.

Relevant disclosures for Rheualt include Chinook/Novartis, Travere, River 3 Renal, Aurinia, Dimerix, and others.

References:

Rheault M, Dell KM, Lieberman KV, et al. Sparsentan (SPAR) vs. Irbesartan (IRB) in Pediatric Patients with FSGS in the Phase 3 DUPLEX Trial. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

Brooks A. FDA Removes Sparsentan (Filspari) Advisory Committee Meeting for FSGS sNDA. Hcplive.com. Published September 10, 2025. Accessed November 8, 2025. https://www.hcplive.com/view/fda-removes-sparsentan-filspari-advisory-committee-meeting-for-fsgs-snda