Sparsentan Shows Benefits Over Irbesartan for IgAN

Sparsentan was granted accelerated approval in the United States for use in adults with primary immunoglobulin A nephropathy (IgAN) based on results of the phase 3 PROTECT trial. The study included 404 patients ≥18 years old with biopsy-proven IgAN, urine protein excretion of ≥1.0 g/day, and estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m². They were randomized 1:1 to receive sparsentan 400 mg/day or irbesartan 300 mg/day for up to 110 weeks.

A group of researchers led by Jonathan Barratt examined efficacy results from the final analysis of the PROTECT double-blind period (approximately 2 years). They presented their findings in an abstract at the International Society of Nephrology World Congress of Nephrology 2024.

At 110 weeks, compared with irbesartan, sparsentan demonstrated sustained reductions in urine protein-to-creatinine ratio (UPCR), with a 40% relative reduction versus irbesartan and long-term kidney function preservation. The results consistently favored sparsentan across subgroups; larger effects were observed with higher baseline proteinuria. In the total study population, treatment with sparsentan led to a statistically significant reduction in the rate of eGFR decline over weeks 6 to 110 (chronic slope) compared with irbesartan (difference, 1.1 mL/min/1.73 m²/year; P=.037). The difference in the rate of eGFR decline from day 1 to week 110 (total slope) with sparsentan versus irbesartan was 1.0 mL/min/1.73 m²/year (P=.058).

In their final analysis, the researchers found that sparsentan had a clinically meaningful benefit on long-term kidney preservation, with absolute change in eGFR and rate of eGFR change favoring sparsentan over irbesartan across baseline proteinuria subgroups over 2 years. “These results may significantly impact the treatment landscape of patients with IgAN,” they said.

Source: KI Reports