Kidney Week

Abstract: TH-PO0452

Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients (Pts) with FSGS Without Nephrotic Syndrome (NS) in the Phase 3 DUPLEX Trial

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

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

Jai Radhakrishnan, MD, MBBS, MS, FASN

• Hernandez, German T., El Paso Kidney Specialists PA, El Paso, Texas, United States

German T. Hernandez, MD, FASN

• Lin, Julie, Travere Therapeutics, Inc., San Diego, California, United States

Julie Lin

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

Radko Komers, MD, PhD

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

Edward Murphy, MS

• Lieberman, Kenneth V., Hackensack University Medical Center, Hackensack, New Jersey, United States

Kenneth V. Lieberman, MD

Background

SPAR is a dual endothelin (ET_A) angiotensin (AT₁) receptor antagonist (DEARA) approved in the US to reduce proteinuria in adult and pediatric (≥8 y) FSGS without NS. As FSGS progression in pts without NS may have greater involvement of maladaptive ET_A- and AT₁-mediated mechanisms than in pts with NS, we assessed SPAR in pts with FSGS without NS in the DUPLEX trial.

Methods

DUPLEX was a 108-wk, randomized study of SPAR (800 mg/d) vs maximum labeled dose IRB (300 mg/d) in pts with FSGS. This post hoc analysis included pts without NS, defined in DUPLEX as those who did not have concurrent (1) proteinuria >3.5 g/day in adults or >2.0 g/g in pediatric pts, (2) serum albumin <3.0 g/dL, and (3) edema, and did not have NS documented in their medical history. Outcomes included changes in urine protein-to-creatinine ratio (UPCR) from baseline, achievement of UPCR <0.3 g/g (complete remission of proteinuria [CR]), <0.7 g/g, or <1.5 g/g at any time on treatment, rate of change in eGFR (chronic slope; wk 6-108; total slope, day 1-wk 108), kidney failure (KF; sustained eGFR <15 mL/min/1.73 m² or initiation of kidney replacement therapy), and safety.

Results

In total, 254 pts (SPAR, 129; IRB, 125) had FSGS without NS. Baseline characteristics were comparable between the SPAR and IRB arms (median UPCR, 2.7 vs 2.8 g/g; median eGFR, 52 vs 50 mL/min/1.73 m²). SPAR led to rapid (within 6 wk) and sustained reductions in UPCR, with a mean change of −48% with SPAR vs −27% with IRB at 108 wk. More pts in the SPAR vs IRB arm achieved CR (20% vs 6%), UPCR <0.7 g/g (43% vs 22%), and <1.5 g/g (79% vs 50%); nominal P<.01 for all thresholds. eGFR declined more slowly with SPAR vs IRB (chronic slope, −3.7 vs −6.2 [difference 2.5] mL/min/1.73 m²/y; total slope, −4.1 vs −6.2 [difference 2.1] mL/min/1.73 m²/y; nominal P<.05 for both). Fewer pts reached KF with SPAR vs IRB (2% vs 8%; nominal P<.05). In pts without NS, SPAR’s safety profile was comparable to IRB, with similar rates of treatment-emergent adverse events (TEAEs; 92% vs 94%) and of TEAEs leading to discontinuation (14% vs 11%) and death (2% vs <1%).

Conclusion

In pts with FSGS without NS, SPAR was well tolerated and led to clinically meaningful reductions in proteinuria, including ≈3× higher CR rates, lower KF rates, and slower eGFR decline vs IRB, supporting the benefit of SPAR in this population.

Funding

• Commercial Support – Travere Therapeutics, Inc.