2-Year Safety, Efficacy of Sparsentan for IgA Nephropathy

The phase 3 PROTECT trial compared sparsentan (SPAR) with irbesartan (IRB) for treating adults with primary IgA nephropathy (IgAN). An interim analysis at week 36 found a significant reduction in proteinuria with SPAR versus IRB (−49.8% vs −15.1%; P<.0001), leading to accelerated approval of SPAR by the US Food and Drug Administration for patients at risk of rapid disease progression. Presenting at the National Kidney Foundation Spring Clinical Meetings, Brad Rovin and colleagues reported on 2-year safety and efficacy data from the trial.

PROTECT is a 110-week trial in adults with biopsy-proven IgAN at risk of progression to kidney failure despite optimized treatment with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, urine protein excretion (UPE) ≥1.0 g/dL, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m². The double-blind, randomized, parallel-group trial compared SPAR 400 mg/dL (n=202) with maximum labeled IRB 300 mg/dL (n=202).

Rovin’s team investigated 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 for SPAR; with it, patients reached CR earlier and more often (31%) versus IRB (11%).

The absolute change in eGFR from baseline to week 110 with SPAR compared with IRB (−5.8 vs −9.5 mL/min/1.73 m²) demonstrated long-term kidney preservation with SPAR (difference, +3.7 mL/min/1.73 m²). Regardless of early treatment discontinuations or disease severity, the eGFR slope favored SPAR. Furthermore, SPAR was associated with minimal changes in BP and was well tolerated.

The researchers concluded that SPAR demonstrated clinically meaningful treatment benefits for preservation of kidney function compared with IRB over a 2-year period. The safety profile of SPAR supported its long-term use.

Source: Rovin B, Barratt J, Murphy E, Geletka R, Perkovic V. Sparsentan (SPAR) shows clinically meaningful treatment effects vs irbesartan (IRB) in patients with IgA nephropathy (IgAN) in the phase 3 PROTECT trial.  Presented at the National Kidney Foundation Spring Clinical Meetings 2024; May 14-18, 2024; Long Beach, California.