Sparsentan-treated patients with immunoglobulin A nephropathy had more clinically meaningful proteinuria improvements than those treated with irbesartan: PROTECT subgroup analysis
Presenter: Laura Kooienga, MD, Colorado Kidney Care, Denver, CO.
Regardless of the baseline proteinuria level in patients with immunoglobulin A nephropathy, sparsentan provided greater clinically meaningful benefits than irbesartan, according to a subgroup analysis of PROTECT study results.
Regardless of baseline proteinuria (urine protein-to-creatinine ratio [UPCR]) in patients with immunoglobulin A nephropathy (IgAN), sparsentan demonstrated greater clinically meaningful benefits than irbesartan in a subgroup analysis of PROTECT study results presented in a Kidney Week 2024 oral presentation.
Previously reported results from the pivotal PROTECT trial showed sustained proteinuria reduction and better kidney function preservation versus the maximum labeled dose of irbesartan in IgAN, stated lead author Laura Kooienga, MD, Colorado Kidney Care, Denver, CO. PROTECT is a double-blind, randomized, active-controlled, phase 3 study conducted at 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe.
The study included patients aged 18 years or older with biopsy-proven primary IgAN and proteinuria of at least 1.0 grams of protein per gram of creatinine (g/g) despite maximized renin-angiotensin system inhibition for at least 12 weeks and with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or below. They were randomly assigned (1:1) to receive either oral sparsentan (target dose 400 mg once daily) or irbesartan (target dose 300 mg once daily).
Dr. Kooienga noted that elevated proteinuria (> 0.5 g/g) is associated with more rapid IgAN disease progression and, thus, proteinuria reduction may lead to improved kidney survival. Dr. Kooienga and colleagues conducted a post hoc analysis of patients in PROTECT with lower and higher baseline UPCRs (< 1.0 g/g vs ≥ 1.0 g/g).
Dr. Kooienga’s analysis included 404 patients (mean age about 47 years; UPCR < 1.0 g/g, n=145; ≥ 1.0 g/g, n=259). Among patients with low baseline UPCR, their change in UPCR from baseline to week 110 was a mean of minus 34.41 (95% confidence interval [CI], minus 46.29 to minus 19.91) for sparsentan and a gain of 13.88 (95% CI, minus 8.31 to plus 41.45) for irbesartan. Among patients with higher baseline UPCR, their change in UPCR from baseline to week 110 was a mean of minus 48.19 for sparsentan (95% CI, minus 55.98 to minus 39.03) and minus 12.53 (95% CI, minus 26.02 to plus 3.43) for irbesartan.
Changes in eGFR from baseline (mL/min/1.73 m2/yr) were smaller for those with lower baseline UPCR: minus 4.1 (95% CI, minus 6.73 to minus 1.57) for sparsentan and minus 6.0 (95% CI, minus 8.83 to minus 3.20) for irbesartan. For those with higher baseline UPCR, results were minus 7.1 (95% CI, minus 9.1 to minus 5.13) for sparsentan and minus 11.3 (95% CI, minus 5.35 to minus 3.61) for irbesartan.
Dr. Kooienga observed that consistent with PROTECT primary results, sparsentan-treated patients experienced a clear treatment benefit as compared with those treated with irbesartan, demonstrating greater reductions in proteinuria and smaller changes in eGFR from baseline to week 110, regardless of baseline UPCR. In addition, sparsentan was generally well tolerated.
“The findings support sparsentan use as a foundational, long-term nephroprotective treatment in patients with IgAN not traditionally considered high risk for disease progression,” Dr. Kooienga concluded.
Funding
- Commercial Support – Travere Therapeutics, Inc.