WB: For IgA Nephropathy-Related Proteinuria, Sparsentan Superior to Irbesartan

Study results indicate that patients with IgA nephropathy reported a 50% reduction in proteinuria at 36 weeks, compared with a 15% reduction in those treated with irbesartan. The rate of complete remission was significantly higher in the sparsentan group.

Study Rundown

IgA nephropathy is the most common cause of primary glomerulonephritis worldwide. Although renin-angioten-sin
blockers (ARBs),such as irbesartan, have been primarily used for treatment, some patients continue to have
persistent proteinuria. Sparsentan, a novel single molecule, angiotensin II receptor antagonist, may have improved efficacy in patients with refractory proteinuria, although existing trials
suggest mixed results. This randomized controlled trial aimed to assess the safety and efficacy of
sparsentan in adults with IgA significantly reduced proteinuria compared with irbesartan. This study was strengthened
by a randomized design with individuals from multiple clinical sites across various countries, thus
increasing its generalizability.

In-Depth [Randomized-Controlled Trial]

Between December 20, 2018 and May 26, 2021, 671 patients were screened for eligibility across 134
clinical sites in 18 countries. Included were patients aged 18 and older with biopsy-confirmed IgA
nephropathy and using angiotensin-converting enzyme (ACE) inhibitor or ARB therapy. Altogether, 404
patients (202 in both the sparsentan and irbesartan groups) were included in the final analysis.
The primary outcome of reduction in urine protein excretion at 36 weeks was significantly greater in the
sparsentan group (-49.8%) than the irbesartan group (-15.1%; geometric least squares mean ratio,
0.59 [95 % CI, 0.51-0.69], P<0.0001).

Similarly, complete remission of proteinuria occurred in 21% of sparsentan patients, com- pared
with 8% of irbesartan patients (OR, 3.1; 95% CI, 1.6-5.8; P=0.0005). Treatment-related adverse
events and change in body weight were comparable between both groups; there were no fatalities.
Overall, findings from this study suggest that sparsentan may be safe and effective for treatment
of proteinuria in patients with biopsy-proven IgA nephropathy.

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