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Abstract: FR-PO0746

Sparsentan (SPAR) vs. Irbesartan (IRB) in Pediatric Patients with FSGS in the Phase 3 DUPLEX Trial

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Rheault, Michelle N., Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis, Minnesota, United States
  • Dell, Katherine MacRae, Center for Pediatric Nephrology and Hypertension, Cleveland Clinic Children’s, Cleveland, Ohio, United States
  • Lieberman, Kenneth V., Pediatric Nephrology, Hackensack University Medical Center, Hackensack, New Jersey, United States
  • Meyers, Kevin E.C., Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Paredes, Ana L., Niklaus Children’s Hospital, Miami, Florida, United States
  • Murphy, Edward, Travere Therapeutics, Inc., San Diego, California, United States
  • Inrig, Jula K., Travere Therapeutics, Inc., San Diego, California, United States
  • Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States
  • Trachtman, Howard, Division of Nephrology, Department of Pediatrics University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • On behalf of the DUPLEX Investigators.
Background

SPAR is a non-immunosuppressive dual endothelin angiotensin receptor antagonist (DEARA) that led to rapid, sustained, and superior proteinuria reductions compared with maximum labeled dose IRB in patients (pts) with FSGS over 108 wks in the phase 3 DUPLEX trial (NCT03493685). Here, we report the impact of SPAR in the subgroup of pediatric pts in DUPLEX.

Methods

DUPLEX was a 108-wk, randomized study of SPAR (800 mg/d for pts >50 kg; 400 mg/d for pts ≤50 kg) vs IRB (300 mg/d for pts >50 kg; 150 mg/d for pts ≤50 kg) in 371 pts with FSGS. Outcomes included UPCR change from baseline, complete remission of proteinuria (CR) and the FSGS partial remission endpoint (FPRE) at any time (CR: UPCR <0.3 g/g; FPRE: UPCR ≤1.5 g/g and >40% reduction from baseline), a composite kidney endpoint (confirmed 40% reduction in eGFR, kidney failure, or death), and safety over the treatment period. This subanalysis included 35 pediatric pts aged <18 y.

Results

Of 35 pediatric pts, 16 received SPAR (median age at informed consent, 14.5 y), and 19 received IRB (median age at informed consent, 14.0 y). Baseline characteristics were comparable between arms (Table). SPAR led to rapid reduction in UPCR that was sustained throughout the study period, with mean reductions of 39.5% with SPAR vs 24.9% with IRB at 108 wks. The proportion of pts achieving CR at any time was 12.5% with SPAR vs 5.3% with IRB and FPRE at any time was 56.3% with SPAR vs 36.8% with IRB (Table). Fewer pts progressed to the composite kidney endpoint with SPAR vs IRB (Table). SPAR had a safety profile that was comparable to IRB; no pts in the SPAR arm and 2 pts in the IRB arm discontinued treatment due to adverse events (Table).

Conclusion

Consistent with findings in the overall DUPLEX population, SPAR was well tolerated and led to rapid and sustained proteinuria reductions vs maximum labeled dose IRB in pediatric pts with FSGS.

Funding

  • Commercial Support – Travere Therapeutics, Inc.

Digital Object Identifier (DOI)