Sparsentan Shows Superior Proteinuria Reduction in Pediatric FSGS Patients Compared to Standard Care
核心洞察
Sparsentan achieved a 39.5% reduction in urine protein-to-creatinine ratio at 108 weeks compared to 24.9% with irbesartan in pediatric FSGS (搜索) patients.
Complete proteinuria remission was achieved by 12.5% of sparsentan-treated patients versus 5.3% with irbesartan, while partial remission occurred in 56.3% versus 36.8% respectively.
The dual endothelin-angiotensin receptor (搜索) antagonist demonstrated a favorable safety profile with no treatment discontinuations due to adverse events.
New subgroup analysis data from the phase 3 DUPLEX trial demonstrate that sparsentan (Filspari), a non-immunosuppressive dual endothelin and angiotensin receptor (搜索) antagonist, achieves superior and sustained reductions in proteinuria compared with irbesartan in pediatric patients with focal segmental glomerulosclerosis (搜索) (FSGS (搜索)). The findings were presented at the American Society of Nephrology (搜索) (ASN) Kidney Week 2025 in Houston.
Trial Design and Patient Population
The parent DUPLEX trial was a 108-week, randomized, active-controlled study that included 371 participants with biopsy-confirmed FSGS (搜索). The pediatric subgroup analysis focused on 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.
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 (搜索) partial remission endpoint (FPRE), and a composite kidney endpoint of ≥40% eGFR decline, kidney failure (搜索), or death.
Sustained Proteinuria Reduction
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. The benefits were evident early in treatment, with urine protein-to-creatinine ratio dropping by a mean 47.5% from baseline at 6 weeks for the sparsentan group compared to 28.5% for the irbesartan group.
Complete remission of proteinuria (UPCR <0.3 g/g) was achieved by 12.5% of sparsentan-treated patients versus 5.3% with irbesartan, while FPRE (UPCR ≤1.5 g/g and >40% reduction) was observed in 56.3% versus 36.8%, respectively.
Renal Protection and Safety Profile
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. Fewer patients in the sparsentan group compared with the irbesartan group had an eGFR reduction of 40% or more, progressed to kidney failure (搜索) or died.
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.
Clinical Significance and Regulatory Timeline
"Based on the recent PARASOL study, reduction of proteinuria is a strong predictor of slowed progression of chronic kidney disease (搜索), so this is a very promising therapy for children who otherwise do not have other options for treatment," said Michelle N. Rheault, MD, director of the division of pediatric nephrology at the University of Minnesota in Minneapolis. "Importantly, the safety profile of sparsentan was similar to irbesartan, a drug we use every day to treat children with kidney disease."
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 (搜索). The agent already boasts approval for use in IgA nephropathy (搜索) dating back to 2023.
Addressing Unmet Medical Need
"Children with FSGS (搜索) are a unique population at high risk of progressing to kidney failure (搜索). Currently available off-label treatments like steroids or calcineurin inhibitors do not work for all patients, and there is a high unmet need for new treatment options," Rheault noted. "I know the patients with FSGS and their families that I see in clinic would be thrilled to have a safe treatment available for them that is not an immune-suppressing medication and can lower the proteinuria so significantly."
The researcher emphasized the importance of these findings for pediatric care: "Children and adults with FSGS (搜索) are treated very differently in clinical practice by pediatric and adult nephrologists. Often, treatments in adults do not translate to treatments that are effective in children due to different disease pathophysiology or different side effect tolerance of the patient and family. In this case, both the adult and pediatric cohorts responded similarly to sparsentan."