Kidney Week

Abstract: FR-OR069

Urinary Biomarker Data from the PROTECT Study in IgAN Demonstrate Renal Anti-Inflammatory Actions of Sparsentan, Including Reduced Macrophage, Complement, and B-Cell Activation Signals

Session Information

• New IgAN Therapies: Subgroups, Outcomes, and Biomarkers
  October 23, 2026 | Location: Room 501, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Barratt, William Alfred, University of Leicester, Leicester, United Kingdom

William Alfred Barratt

• Cheung, Chee Kay, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

Chee Kay Cheung, MBChB, PhD

• Thomas, Roisin Clare, University of Leicester, Leicester, United Kingdom

Roisin Clare Thomas, PhD

• Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States

Radko Komers, MD, PhD

• Kusibab, Kristie, Travere Therapeutics, Inc., San Diego, California, United States

Kristie Kusibab, MS

• Hendry, Bruce, Travere Therapeutics, Inc., San Diego, California, United States

Bruce Hendry

• Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden

Alex Mercer, PhD

• Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States

Donald E. Kohan, MD, PhD, FASN

• Rovin, Brad, Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad Rovin, MD, FASN

• Lafayette, Richard A., Stanford Hospital and Clinics, Stanford, Connecticut, United States

Richard A. Lafayette, MD

• Barratt, Jonathan, University of Leicester and Leicester General Hospital, Leicester, United Kingdom

Jonathan Barratt, MBChB, PhD

Background

Sparsentan (SPAR), a non-immunosuppressive dual endothelin angiotensin receptor antagonist (DEARA), is approved in the US and Europe for adults with primary IgA nephropathy (IgAN) at risk of disease progression. Approval was based on PROTECT (NCT03762850), which showed superior proteinuria reduction and kidney function preservation over 2 years vs maximum labeled dose irbesartan (IRB). In the phase 2, single-arm, open-label SPARTAN study, SPAR reduced urinary biomarkers of immune cell activation, inflammation, and complement injury (including sCD163, BAFF, C5b-9, and IL-6) in 11 patients with IgAN, making these biomarkers highly relevant for understanding and tracking disease progression in IgAN. Here we report the impact of SPAR on these 4 biomarkers vs IRB in the larger, randomized, double-blind PROTECT trial.

Methods

PROTECT was a multicenter, randomized (1:1) trial of adults with biopsy-proven IgAN assigned to SPAR 400 mg/d or IRB 300 mg/d for up to 110 wk. Patients had urine protein excretion ≥1.0 g/d and estimated glomerular filtration rate ≥30 mL/min/1.73 m² despite optimized RAS inhibitor therapy. We report change from baseline in urinary biomarkers measured by ELISA, normalized to creatinine, and analyzed using a mixed model for repeated measures.

Results

SPAR demonstrated statistically significant reductions from baseline at week 110 across all 4 urinary biomarkers (Table). These reductions were statistically significantly greater than those seen with maximum labeled dose IRB across all 4 urinary biomarkers.

Conclusion

SPAR showed rapid and sustained reductions in urinary biomarkers of inflammation, BAFF, and inhibition of complement activation vs maximum labeled dose IRB in patients with IgAN in PROTECT, indicating anti-inflammatory benefits of targeting endothelin and angiotensin pathways in the treatment of IgAN.

Funding

• Commercial Support – Travere Therapeutics, Inc.