Sparsentan Versus Irbesartan in Pediatric Patients With FSGS

Area of Science:

• Nephrology
• Pediatric Nephrology
• Clinical Pharmacology

Background:

• Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome in children, often progressing to kidney failure.
• Current treatments for FSGS have limitations, highlighting the need for novel therapeutic strategies.
• Sparsentan, a dual endothelin angiotensin receptor antagonist, has shown promise in reducing proteinuria in adults with FSGS.

Purpose of the Study:

• To evaluate the efficacy and safety of sparsentan in pediatric patients with FSGS.
• To compare the effects of sparsentan versus irbesartan on proteinuria reduction and remission rates in children.
• To assess the long-term outcomes and tolerability of sparsentan in this specific population.

Main Methods:

• A post hoc analysis of the phase 3 DUPLEX trial (NCT03493685) involving pediatric patients (8 to <18 years).
• Patients were randomized to receive either sparsentan or irbesartan (maximum labeled dose) for 108 weeks.
• Key outcomes included changes in urine protein-to-creatinine ratio (UPCR), rates of complete remission (CR), FSGS partial remission, and safety assessments.

Main Results:

• Sparsentan demonstrated rapid and sustained reductions in UPCR from week 6 through 108 (mean reduction 39.5% vs. 24.9% for irbesartan).
• Higher rates of complete remission (12.5% vs. 5.3%) and FSGS partial remission (56.3% vs. 36.8%) were observed in the sparsentan group.
• Sparsentan and irbesartan exhibited similar safety profiles, with comparable adverse event incidence and severity.

Conclusions:

• Sparsentan is effective in achieving clinically meaningful proteinuria reductions in pediatric patients with FSGS.
• The drug is generally well-tolerated in children, with a safety profile consistent with the overall DUPLEX trial population.
• These findings support sparsentan as a potential treatment option for pediatric FSGS, offering an alternative to existing therapies.