Safety and effectiveness of sparsentan/sparsentan in the treatment of IgA nephropathy

The phase 3 PROTECT trial compared sparsentan/sparsentan (SPAR; Sparsentan) with irbesartan (IRB; irbesartan) in adults with primary IgA nephropathy (IgAN). An interim analysis at week 36 found a significant reduction in proteinuria in the sparsentan group compared with the irbesartan group (-49.8% vs. -15.1%; P<0.0001), resulting in the U.S. Food and Drug Administration (FDA)’s accelerated approval of sparsentane for patients at risk for rapid disease progression.

PROTECT was a 110-week trial in adults with biopsy-confirmed IgAN who were at risk for progression to renal failure, had urinary protein excretion (UPE) ≥1.0 g/dL and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite optimal treatment with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker. The double-blind, randomized, parallel-group trial compared sparsentan 400 mg/dL (n = 202) with irbesartan maximal label 300 mg/dL (n = 202), investigating complete remission of proteinuria (CR; UPE <0.3 g/d), absolute change in eGFR, rate of eGFR change (slope), and blood pressure (BP) outcomes. Results were more positive with sparsantan; patients achieved CR earlier and more frequently (31%) compared with irbesartan (11%).

The absolute change in eGFR from baseline to week 110 (-5.8 vs -9.5mL/min/1.73m2) demonstrated the long-term renoprotective effect of sparsentan (difference +3.7mL/min/1.75m2) compared with irbesartan. Regardless of early treatment discontinuation or disease severity, the eGFR slope favored sparsentane. Additionally, sparsentane was associated with minimal changes in blood pressure and was well tolerated.

The investigators concluded that sparsentandemonstrated a clinically meaningful therapeutic benefit in protecting renal function compared withirbesartan over2 years. Sparsentine's safety features support its long-term use.