Patients in DUPLEX Achieved Partial or Complete Remission of Proteinuria Earlier and More Often With Sparsentan vs Irbesartan: Implications for Slowing Progression to Kidney Failure in Focal Segmental Glomerulosclerosis (FSGS)
2025
Patients With Focal Segmental Glomerulosclerosis (FSGS) Reach Proteinuria <0.7 g/g More Often With Sparsentan vs Irbesartan in DUPLEX: Implications for Kidney Failure Risk
Poster
Published on November 6, 2025
About the research
Summary
Background
- Sparsentan is a non-immunosuppressive Dual Endothelin Angiotensin Receptor Antagonist (DEARA) that led to rapid and sustained proteinuria reduction vs. irbesartan in patients with focal segmental glomerulosclerosis (FSGS) in the Phase 3 DUPLEX trial, with similar observed safety profiles1-3
- Across a range of urine protein-to-creatinine ratio (UPCR) thresholds, the PARASOL initiative identified UPCR <0.7 g/g as a clinically meaningful low proteinuria target that is associated with lower risk of kidney failure in patients with FSGS1,4
Aim
To assess1:
- The impact of sparsentan vs. irbesartan on achieving the low proteinuria threshold of UPCR <0.7 g/g
- The effect of reaching UPCR <0.7 g/g on observed kidney failure rates in the DUPLEX trial
- The implications of reaching UPCR <0.7 g/g on long-term kidney failure risk using real-world registry data from the UK National Registry of Rare Kidney Disease (RaDaR)
Approach
DUPLEX was a Phase 3, multicenter, double-blind, randomized trial that assessed the efficacy and safety of 800 mg/day sparsentan (n=184) versus maximum labeled dose irbesartan (n=187) in biopsy-proven or genetic FSGS without known secondary causes2
In this post hoc analysis, observed outcomes over the 108-week double-blind study period included1:
- Proportion of adult patients reaching UPCR <0.7 g/g in the sparsentan vs. irbesartan treatment arms
- Rates of kidney failure, defined as sustained estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 or kidney replacement therapy (KRT) by proteinuria response (irrespective of treatment)
The impact of achieving UPCR <0.7 g/g on long-term kidney failure risk was assessed in a cohort of patients with FSGS from RaDaR who aligned with the DUPLEX trial entry criteria and baseline characteristics over 60 months (following 24 months of pre-response)1
Key findings
Throughout the 108 weeks of the DUPLEX trial, patients in the sparsentan arm achieved UPCR <0.7 g/g earlier and more often than those in the irbesartan arm (37.5% vs. 21.4%, respectively)1
Irrespective of treatment, patients who achieved UPCR <0.7 g/g at any time in the DUPLEX trial were less likely to reach kidney failure than those who did not reach this threshold (3.6% vs. 11.2%, respectively)1
The RaDaR cohort (n=386) was comparable to the previously described DUPLEX study population1
In the DUPLEX-aligned RaDaR cohort, patients who achieved UPCR <0.7 g/g at 24 months had lower risk of kidney failure over the next 60 months than those who did not reach this threshold (survival probability estimate 0.94 vs. 0.66, respectively)1
- Similarly, the 60-month kidney failure risk for patients who reached UPCR <0.7 g/g at any time over 24 months was lower compared with those who did not reach this threshold1
Conclusions
In the DUPLEX trial, patients with FSGS achieved the low proteinuria threshold of UPCR <0.7 g/g earlier and more often with
800 mg/day sparsentan vs. maximum labeled dose irbesartan1
Patients who achieved UPCR <0.7 g/g were less likely to progress to kidney failure than those who did not achieve this low proteinuria threshold over the 108-week DUPLEX study1
In a cohort from RaDaR aligned to the DUPLEX study population, patients who achieved UPCR <0.7 g/g over 24 months had a lower risk of kidney failure over the next 60 months, consistent with results from PARASOL1,4
Related content
Footnotes
DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; KRT, kidney replacement therapy; RaDaR; UK National Registry of Rare Kidney Disease; UPCR, urine protein-to-creatinine ratio.
- Radhakrishnan J et al. Poster presented at: American Society of Nephrology Kidney Week 2025; November 6-9, 2025; Houston, TX. TH-PO1219.
- Rheault MN, et al. N Eng J Med. 2023;389(26):2436-2445.
- Trachtman H. Expert Rev Clin Immunol. 2024;20(6):571-576.
- Smith A. Presented at: American Society of Nephrology Kidney Week 2024; October 23-27, 2024; San Diego, CA. Abstract INFO10-SA.
MA-SP-25-0213 | November 2025