Abstract: TH-PO1219
Patients (Pts) with FSGS Reach Proteinuria <0.7 g/g More Often with Sparsentan (SPAR) vs. Irbesartan (IRB) in DUPLEX: Implications for Kidney Failure (KF) Risk
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Radhakrishnan, Jai, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, United States
- Gale, Daniel P., University College London, London, England, United Kingdom
- Gbadegesin, Rasheed A., Duke University Medical Center, Durham, North Carolina, United States
- Inrig, Jula K., Travere Therapeutics, Inc., San Diego, California, United States
- Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States
- Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
- Murphy, Edward, Travere Therapeutics, Inc., San Diego, California, United States
- Pitcher, David, National Registry of Rare Kidney Diseases, UK Kidney Association, Bristol, United Kingdom
- Saleem, Moin A., University of Bristol, Bristol, England, United Kingdom
Background
SPAR, a dual endothelin angiotensin receptor antagonist (DEARA), led to rapid and sustained proteinuria reduction vs IRB in pts with FSGS in the phase 3 DUPLEX trial. The PARASOL initiative identified urine protein-to-creatinine ratio (UPCR) <0.7 g/g as a clinically meaningful low proteinuria threshold in FSGS. We assessed the impact of SPAR vs IRB on achieving UPCR <0.7 g/g and its implications for progression to KF.
Methods
DUPLEX (NCT03493685) is a 108-wk randomized trial of the efficacy and safety of SPAR (n=184; 800 mg/d) vs IRB (n=187; 300 mg/d) in FSGS. We assessed the proportion of pts reaching UPCR <0.7 g/g with SPAR vs IRB and, irrespective of treatment, the effect of reaching UPCR <0.7 g/g at any time on progression to KF (sustained eGFR <15 mL/min/1.73 m2 or kidney replacement therapy). In a cohort of pts with biopsy-proven or genetic FSGS (n=386) from the UK National Registry of Rare Kidney Diseases (RaDaR) aligned with DUPLEX entry criteria and baseline characteristics (8-75 y of age, eGFR ≥25 mL/min/1.73 m2, first UPCR ≥1.5 g/g ≥6 mo from diagnosis), we estimated the impact of achieving UPCR <0.7 g/g during a 24-mo period on KF risk over an additional 60 mo.
Results
In DUPLEX, pts treated with SPAR vs IRB achieved UPCR <0.7 g/g earlier (P<.0001) and more often, with 19% vs 11% (relative risk [RR], 1.7 [95% CI, 1.0-2.7]) reaching UPCR <0.7 g/g at 108 wk and 38% vs 23% (RR, 1.7 [1.2-2.3]) at any time. Irrespective of treatment, pts reaching UPCR <0.7 g/g at any time were less likely to reach KF vs pts who did not (3.6% vs 11.2%; RR, 0.52 [0.2-1.8]) during the 108-wk trial. In the RaDaR cohort, achieving UPCR <0.7 g/g at 24 mo was associated with lower risk of KF over an additional 60 mo of follow-up (hazard ratio [HR], 0.13 [95% CI, 0.1-0.4]), as was achieving UPCR <0.7 g/g at any time over 24 mo (HR, 0.28 [0.17-0.46]).
Conclusion
In DUPLEX, pts with FSGS achieved UPCR <0.7 g/g earlier and more often with SPAR vs IRB. Together, clinical trial and real-world data indicate that reaching UPCR <0.7 g/g is associated with clinically meaningful reductions in KF risk both in the near- and long-term, supporting the long-term benefit of SPAR’s anti-proteinuric effect.
Funding
- Commercial Support – Travere Therapeutics, Inc.