Jonathan Barratt, MD: PROTECT Subgroup Analyses Continue to Favor Sparsentan for IgAN

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Barratt discusses results from subgroup analyses of the phase 3 PROTECT trial based on baseline proteinuria and what they add to previous findings.

Subgroup analyses of the phase 3 PROTECT trial highlight sparsentan’s clinically meaningful benefit over irbesartan for long-term kidney preservation, absolute change in estimated glomerular filtration rate (eGFR), and rate of eGFR change in adult patients with primary IgA nephropathy across baseline proteinuria subgroups over 2 years.1

Findings were presented at the World Congress of Nephrology in Buenos Aires, Argentina, on April 15, 2024, complementing initial 2-year findings presented last year in a late-breaking oral presentation at the American Society of Nephrology Kidney Week 2023, which provided evidence suggesting use of sparsentan was associated with a more significant antiproteinuric effect at 110 weeks, confirmed by chronic and total eGFR slope, relative to use of irbesartan in patients with IgAN.1,2

“The data is very much more looking at subgroup analyses. It doesn't detract. In fact, it reinforces the value of sparsentan with dual ARB ERA blockade in managing IgA nephropathy, so it's supportive data,” Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, said in an interview with HCPLive. “We've had the headline data already, so it's not going to change that in any way.”

A dual endothelin type A and angiotensin II type 1 receptor antagonist, sparsentan received accelerated approval for reducing proteinuria in adults with primary IgAN in February 2023, making it the first and only non-immunosuppressive treatment targeting glomerular injury in the kidney to reduce proteinuria in this patient population at risk of rapid disease progression. On March 11, 2024, Travere Therapeutics submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for conversion of the existing accelerated approval to full approval, based on 2-year confirmatory results from PROTECT in which sparsentan demonstrated long-term kidney function preservation and achieved a significant reduction in proteinuria and a clinically meaningful difference in eGFR slope versus an active comparator, irbesartan.2,3

“The bottom line is, if we're talking about sparsentan and itapcopan, they are completely complimentary and they do completely different things. In where we are heading in terms of IgA therapeutics, those are drugs I would be wanting to think about using together alongside a drug that targets pathogenic IgA production,” Barratt explained.

Findings presented at the World Congress of Nephrology showed sparsentan outperformed irbesartan for complete proteinuria remission, defined as urine protein excretion < 0.3 g/day, (31% vs 11%; RR, 2.5; 95% CI, 1.6 to 4.1), as well as for change in eGFR mL/min/1.73m2 (-5.8 vs -9.5; 95% CI, 1.5 to 6.0). Results also showed sparsentan (17.4 years) had a greater potential long–term impact of improved eGFR slope on time to dialysis, besting both irbesartan (12.4 years) and renin-angiotensin system inhibitor standard of care (8.9 years).1

Serious treatment-emergent adverse events were comparable between the groups (37% vs 35%), with no drug-induced liver injury in the sparsentan group. Additional subgroup analyses by urine protein-to-creatinine ratio revealed sparsentan was favored across all subgroups for absolute change in eGFR by baseline proteinuria.1


  1. Barratt J, et al. Sparsentan vs Irbesartan in Patients with IgAN: Subgroup Analyses of 2-Year Results from the Pivotal Phase 3 PROTECT Trial. Presented at: World Congress of Nephrology (WCN) 2024 Annual Scientific Session. April 13 – 16, 2024. Buenos Aires, Argentina.
  2. Campbell P. PROTECT: Sparsentan Outperforms Irbesartan in IgA Nephropathy HCPLive. November 3, 2023. Accessed April 16, 2024.
  3. Travere Therapuetics. Travere Therapeutics Submits Supplemental New Drug Application to the U.S. Food and Drug Administration Seeking Full Approval of FILSPARI® (sparsentan) for the Treatment of IgA Nephropathy (IgAN). March 11, 2024. Accessed April 16, 2023.