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Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: TH-PO1199

Outcomes of the DUPLEX Trial in Patients with Genetic Focal Segmental Glomerulosclerosis (gFSGS)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Lai Yee, Jennifer, University of Michigan, Ann Arbor, Michigan, United States
  • Gong, Wu, Travere Therapeutics, Inc., San Diego, California, United States
  • Inrig, Jula K., Travere Therapeutics, Inc., San Diego, California, United States
  • Rheault, Michelle N., University of Minnesota Medical School, Minneapolis, Minnesota, United States
  • Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States
  • Trachtman, Howard, University of Michigan, Ann Arbor, Michigan, United States
Background

gFSGS, caused by mutations in podocyte genes, is generally refractory to most available treatments. The DUPLEX trial evaluated the efficacy and safety of sparsentan (SPAR) vs irbesartan (IRB) in patients with FSGS. Overall, the trial showed a greater reduction of proteinuria with SPAR treatment; however, it is uncertain if SPAR’s efficacy varies by underlying pathogenesis. Therefore, this post hoc analysis aims to assess the efficacy of SPAR in the subset of DUPLEX patients with gFSGS.

Methods

A total of 355 study patients were genotyped by the FSGS panel of Prevention Genetics. Patients with pathogenic or likely pathogenic variants in podocyte genes were classified to have gFSGS with Mendelian inheritance. The outcome analysis examined changes in proteinuria (percentage reduction; achieving complete remission [CR; urine protein-to-creatinine ratio <0.3 g/g at any time]) and proportion of patients reaching end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, dialysis, or transplant) with SPAR vs IRB.

Results

Overall, 8.7% (n=31) were identified to have gFSGS. At baseline, patients with gFSGS were younger and had higher eGFR vs the overall DUPLEX population, and most had nephrotic-range proteinuria. SPAR showed a more rapid and more pronounced reduction in proteinuria vs IRB, and this effect was sustained (Table). The same pattern was observed in the subset of patients with NPHS2 mutations. CR was achieved only in SPAR-treated patients with gFSGS (n=1 [8%] vs n=0), whereas reaching ESKD was more frequent with IRB (n=3 [17%] vs n=1 [8%]).

Conclusion

There was more pronounced early antiproteinuric response to SPAR vs IRB in patients with gFSGS that was sustained over the treatment period. The findings support a recommendation for SPAR administration to reduce proteinuria and achieve long-term kidney health benefits in this high-risk group of patients with gFSGS.

Outcomes
All gFSGSSPAR (n=13)IRB (n=18)
Reduction in proteinuria, %*Week 12−53 (−67 to −33)−25 (−44 to 2)
 Week 36−63 (−74 to −48)−35 (−52 to −12)
 Week 108−49 (−66 to −23)−27 (−49 to 3)
Complete remission, n (%)At any time1 (8)0 (0)
ESKD, n (%)At any time1 (8)3 (17)
ESKD, end-stage kidney disease; gFSGS, genetic focal segmental glomerulosclerosis; IRB, irbesartan; LS, least square; SPAR, sparsentan.
*Geometric LS Mean Percent Change from Baseline (95% CI).

Funding

  • Commercial Support – Travere Therapeutics, Inc.