Sparsentan outperforms irbesartan for treatment of IgAN

Sparsentan met all primary and secondary endpoints for the treatment of patients with immunoglobulin A nephropathy (IgAN). Sparsentan reduced proteinuria and slowed the rate of estimated glomerular flow rate (eGFR) decline.

Patients with IgAN have an activated endothelin and renin-angiotensin-aldosterone system, involved in kidney fibrosis and inflammation. “We postulated that treatment with sparsentan, a dual endothelin and angiotensin receptor antagonist, would be more effective in reducing proteinuria and preserving kidney function in patients with IgAN than treatment with an angiotensin receptor blocker alone,” said Prof. Brad Rovin (Ohio State University, OH, USA) [1,2].

The PROTECT trial (NCT03762850) was a phase 3, double-blind trial that randomised participants 1:1 to sparsentan (n=202) or irbesartan (n=202) for 110 weeks. The primary endpoint was a change in urine protein creatinine ratio (UPCR) at week 36. The secondary endpoint was a change in eGFR measured by chronic and total eGFR slope.

At week 36, participants receiving sparsentan had a 41% relative reduction in proteinuria compared with those receiving irbesartan (least squares mean ratio 0.59; 95% CI 0.51–0.69; P<0.0001), and that difference was maintained throughout the 110 weeks. More patients receiving sparsentan achieved complete proteinuria remission (i.e. <0.3 g/day) than those receiving irbesartan (31% vs 11%). eGFR slope declined less in the sparsentan group (-2.7 mL/min/1.73 m²/year; 95% CI -3.4 to -2.1) than in the irbesartan group (-3.8 mL/min/1.73 m²/year; 95% CI -4.6 to -3.1), and this difference was statistically significant (P=0.037).

Using a composite kidney failure endpoint of a 40% reduction of eGFR, end-stage kidney disease, or death, sparsentan outperformed irbesartan (RR 0.68; 95% CI 0.4–1.2). Irbesartan-treated participants were also more likely to start immunosuppressive therapy during the trial (OR 2.87; 95% CI 1.09–7.57). Adverse events were similar between the 2 groups.

Overall, the PROTECT trial met its primary endpoints and showed favourable outcomes for sparsentan compared with irbesartan in all its endpoints.

1. Rovin BH, et al. Pivotal Results of the Phase 3 PROTECT Trial of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with Immunoglobulin A Nephropathy (IgAN). FR-OR109, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.
2. Rovin BH, et al. Lancet. 2023;Nov 3. DOI:1016/S0140-6736(23)02302-4.

 

Copyright ©️2023 Medicom Medical Publishers



Posted on 28 November, 202327 March, 2024