Abstract: FR-PO0839
Sparsentan (SPAR) in Participants with FSGS and Collagen Type IV Alpha 3-5 Chain (COL4A3-5) Variants
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 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
- Lai Yee, Jennifer, University of Michigan, Ann Arbor, Michigan, United States
- Trachtman, Howard, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States
- Rheault, Michelle N., Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Bedard, Patricia W., PW Bedard Consulting, San Diego, California, United States
- Gruber, Angela J, PreventionGenetics, Marshfield, Wisconsin, United States
- Gong, Wu, Travere Therapeutics, Inc., San Diego, California, United States
- Komers, Radko, Travere Therapeutics, Inc., San Diego, California, United States
Background
In DUPLEX, SPAR led to sustained proteinuria reductions vs irbesartan (IRB) in participants with FSGS that were consistent in participants with podocyte gene mutations. We report the impact of SPAR in participants with FSGS and a spectrum of COL4A3-5 pathogenic variants.
Methods
DUPLEX (NCT03493685) was a 108-week, randomized study of SPAR (800 mg/d) vs IRB (300 mg/d) in participants with FSGS. A post hoc exploratory analysis was conducted on the subgroup of participants with COL4A3-5 pathogenic variants identified on a 73-gene FSGS panel (355/371 participants in DUPLEX were sequenced). Outcomes included change from baseline in urine protein-to-creatinine ratio (UPCR), complete remission (CR) of proteinuria (UPCR <0.3 g/g), and the composite kidney endpoint of 40% decline in estimated glomerular filtration rate (eGFR), progression to kidney failure, or death.
Results
Of sequenced participants, 25 (7%) had a COL4A3-5 likely pathogenic/pathogenic variant (SPAR, n=11; IRB, n=14). Baseline characteristics were comparable between arms (Table). Compared to IRB, SPAR-treated participants had greater and more rapid reductions in UPCR throughout the study (Figure), with 2 achieving CR of proteinuria at any time with SPAR vs 1 with IRB. Fewer participants progressed to the composite kidney endpoint with SPAR vs IRB (Table).
Conclusion
Consistent with the overall DUPLEX population, participants with FSGS and COL4A3-5 variants had more pronounced and durable proteinuria reductions with SPAR vs IRB. While long-term follow-up and larger sample sizes are needed to further assess SPAR’s impact in this population, findings suggest SPAR could have a meaningful impact in participants with COL4A3-5 variants, a group for which there are no approved therapies.
Funding
- Commercial Support – Travere Therapeutics, Inc.