Sparsentan Versus Irbesartan in Pediatric Patients With FSGS

Sparsentan, a nonimmunosuppressive dual endothelin angiotensin receptor antagonist, led to rapid and sustained proteinuria reductions versus maximum labeled dose irbesartan in patients with focal segmental glomerulosclerosis (FSGS) in the phase 3 DUPLEX trial (NCT03493685). Here, we describe the efficacy and safety of sparsentan in the pediatric patients enrolled in DUPLEX.

DUPLEX was a 108-week randomized trial of sparsentan versus irbesartan (active control) in patients with FSGS (excluding known secondary causes). A post hoc analysis assessed efficacy and safety in the pediatric subgroup (8 to < 18 years). Outcomes included proteinuria (urine protein-to-creatinine ratio [UPCR]) changes from baseline; rates of complete remission (CR) of proteinuria (UPCR of < 0.3 g/g); FSGS partial remission end point (UPCR of ≤ 1.5 g/g and > 40% reduction from baseline); UPCR of < 0.5, < 0.7, or < 1.0 g/g at any time; rates of kidney failure; and safety.

Thirty-five pediatric patients received sparsentan (n = 16) or irbesartan (n = 19). UPCR reductions were observed as early as week 6 and sustained through 108 weeks (mean reduction at 108 weeks: sparsentan, 39.5% vs. irbesartan, 24.9%). More patients in the sparsentan arm than the irbesartan arm achieved low proteinuria thresholds, including CR (12.5% vs. 5.3%) and the FSGS partial remission end point (56.3% vs. 36.8%). Sparsentan and irbesartan had similar safety profiles, with comparable incidence and severity of adverse events.

In this post hoc analysis of pediatric patients with FSGS, sparsentan was generally well tolerated and clinically meaningful reductions in proteinuria were observed, consistent with the overall DUPLEX population.