Kidney Week

Abstract: FR-OR57

PROTECT Subgroup Analysis: Clinical Benefits of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with IgAN Who Have Proteinuria above and below 1 g/g

Session Information

• IgA Nephropathy: New Therapies and Insights
  October 25, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States

Laura Kooienga, MD

• Trimarchi, Hernan, Nephrology Service, British Hospital of Buenos Aires, Buenos Aires, Argentina

Hernan Trimarchi, MD, PhD, FASN

• Floege, Jürgen, Division of Nephrology, RWTH Aachen University Hospital, Aachen, Germany

Jürgen Floege, MD

• Preciado, Priscila, Travere Therapeutics, Inc., San Diego, California, United States

Priscila Preciado, MD

• Murphy, Edward, Travere Therapeutics, Inc., San Diego, California, United States

Edward Murphy, MS

• Radhakrishnan, Jai, Division of Nephrology, Colombia University Irving Medical Center, New York, New York, United States

Jai Radhakrishnan, MD, MBBS, MS, FASN

Group or Team Name

• On behalf of the DUPRO Steering Committee and PROTECT Investigators.

Background

SPAR is a nonimmunosuppressive, dual endothelin angiotensin receptor antagonist (DEARA) approved in the US and EU for adults with IgAN. In the pivotal PROTECT trial, SPAR showed sustained proteinuria reduction and better kidney function preservation vs the maximum labeled dose of IRB. Elevated proteinuria (>0.5 g/day) is associated with more rapid disease progression, and proteinuria reduction may lead to improved kidney survival. A post hoc analysis of pts in PROTECT with urine protein-to-creatinine ratio (UPCR) of <1.0 vs ≥1.0 g/g at baseline is presented.

Methods

PROTECT was a 110-week, double-blind, randomized (1:1) trial of SPAR (400 mg) vs active control IRB (300 mg) in adults with biopsy-proven IgAN, urine protein excretion of ≥1.0 g/day despite maximized renin-angiotensin system inhibition for ≥12 weeks, and estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m². We report treatment effects in pt subgroups with UPCR of <1.0 vs ≥1.0 g/g at baseline.

Results

This analysis included 404 pts (UPCR: <1.0 g/g, n=145; ≥1.0 g/g, n=259). Baseline characteristics were well balanced between treatment arms (Table). Consistent with primary results, SPAR-treated pts showed a clear treatment benefit vs IRB, with a greater proteinuria reduction and smaller change in eGFR from baseline to week 110, regardless of baseline UPCR. SPAR was generally well tolerated.

Conclusion

SPAR showed clinically meaningful benefits vs IRB across baseline UPCR, supporting its use as a foundational, long-term nephroprotective treatment in pts with IgAN not traditionally considered high risk for disease progression.

Funding

• Commercial Support – Travere Therapeutics, Inc.