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
American Society of Nephrology (ASN) Kidney Week – 2025
In DUPLEX, Patients With Focal Segmental Glomerulosclerosis (FSGS) Reached Low Proteinuria More Often With Sparsentan vs. Irbesartan Regardless of Baseline Proteinuria
Poster
Published on May 6, 2026
Contributors
Radhakrishnan J, Hernandez GT, Inrig J et al.
Radhakrishnan J, Hernandez GT, Inrig J et al.
About the research
Summary
Background
- In patients with FSGS, elevated proteinuria is associated with an increased risk of progression to kidney failure, whereas low proteinuria across a range of urine protein-to-creatinine (UPCR) thresholds is associated with a lower risk of kidney failure1,2
- Sparsentan led to rapid and sustained reductions in proteinuria vs. maximum-labeled dose irbesartan in patients with FSGS in the Phase 3 DUPLEX trial and was well tolerated with a comparable safety profile1,3
- Sparsentan is a Dual Endothelin Angiotensin Receptor Antagonist (DEARA) indicated to reduce proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome1,4-6
- Nephrotic syndrome includes the presence of three concurrent criteria: proteinuria greater than 3.5 g/24h (adults) or UPCR >2.0 g/g (pediatric patients <18 years of age), serum albumin <3.0 g/dL, and edema6
Aim
The aim of this post hoc, exploratory subgroup analysis of the Phase 3 DUPLEX trial was to determine the treatment effects of sparsentan vs. maximum-labeled dose irbesartan in patients with FSGS with baseline UPCR <3.0 g/g and ≥3.0 g/g1
Figure. DUPLEX study design and post hoc analysis1
DUPLEX is a Phase 3, randomized, double-blind trial studying the efficacy and safety of sparsentan vs. active control, maximum-labeled dose irbesartan in adults and children (aged ≥8 years) with FSGS1
Patients were randomized 1:1 to receive sparsentan or irbesartan. During the double-blind period, doses were titrated to the target doses of 800 mg/d of sparsentan or 300 mg/d of irbesartan after 2 weeks of 400 mg/d of sparsentan or 150 mg/d of irbesartan (patients weighing ≤50 kg received half the otherwise specified doses). After 108 weeks, patients resumed SOC treatment, including RASi, with the exception of irbesartan1
Key findings
Within each subgroup, patient demographics and baseline characteristics were generally balanced between treatment arms1
While there were more pediatric patients in the ≥3.0 g/g subgroup compared to the <3.0 g/g subgroup, the proportions of pediatric patients were similar between treatment arms across baseline proteinuria subgroups1
Sparsentan showed rapid and sustained reductions in proteinuria across baseline proteinuria subgroups through Week 108, compared with maximum-labeled dose irbesartan1
Figure. LS mean change in UPCR from baseline in populations with UPCR <3 g/g and UPCR ≥3 g/g
Through Week 108, sparsentan sustained greater reductions in proteinuria vs. maximum-labeled dose irbesartan1
Among patients with baseline UPCR <3.0 g/g, UPCR was reduced by 48% over 108 weeks with sparsentan vs. 24.9% with maximum-labeled dose irbesartan1
Among patients with baseline UPCR ≥3.0 g/g, UPCR was reduced by 51.8% over 108 weeks with sparsentan vs. 39.8% with maximum-labeled dose irbesartan1
Irrespective of baseline UPCR subgroup, sparsentan demonstrated consistent reductions in proteinuria across low proteinuria thresholds (<0.3 g/g, <0.7 g/g, and <1.5 g/g) vs. maximum-labeled dose irbesartan1
Figure. Achievement of low proteinuria thresholds1
Patients achieved low proteinuria thresholds at any time more often with sparsentan vs. maximum-labeled dose irbesartan1
Achievement of low proteinuria thresholds at any time among patients with baseline UPCR <3.0 g/g1:
- UPCR <0.3 g/g (sparsentan vs. maximum-labeled dose irbesartan): 14.9% vs. 6.5% (Relative risk [RR]: 2.15, 95% confidence interval [CI]: 0.87-5.33)
- UPCR <0.7 g/g (sparsentan vs. maximum-labeled dose irbesartan): 40.2% vs. 22.6% (RR: 1.75, 95% CI: 1.11-2.77)
- UPCR <1.5 g/g (sparsentan vs. maximum-labeled dose irbesartan): 79.3% vs. 52.7% (RR: 1.50, 95% CI: 1.21-1.87)
Achievement of low proteinuria thresholds at any time among patients with baseline UPCR ≥3.0 g/g1:
- UPCR <0.3 g/g (sparsentan vs. maximum-labeled dose irbesartan): 6.2% vs. 3.2% (RR: 1.90, 95% CI: 0.50-7.16)
- UPCR <0.7 g/g (sparsentan vs. maximum-labeled dose irbesartan):19.6% vs. 9.6% (RR: 2.03, 95% CI: 0.99-4.16)
- UPCR <1.5 g/g (sparsentan vs. maximum-labeled dose irbesartan): 34.0% vs. 20.2% (RR: 1.64, 95% CI: 1.04-2.58)
Sparsentan was well tolerated with a consistent safety profile across baseline proteinuria subgroups1
The most common treatment-emergent adverse events (TEAEs ≥15% of patients in any group) included1:
- Chronic kidney disease
- COVID-19*
- Diarrhea
- Headache
- Hyperkalemia
- Hypotension
- Muscle spasms
- Peripheral edema
- Urinary tract infection
Table. Adverse events1
Among patients with baseline UPCR of <3.0 g/g, TEAEs were experienced by 93% (81/87) of patients with sparsentan and 90% (84/93) of patients with maximum-labeled dose irbesartan1
Among patients with baseline UPCR ≥3.0 g/g, TEAEs were experienced by 94% (91/97) of patients with sparsentan and 96% (90/94) of patients with maximum-labeled dose irbesartan1
Among patients with baseline UPCR of <3.0 g/g, serious TEAEs were experienced by 39% (34/87) of patients with sparsentan and 34% (32/93) of patients with maximum-labeled dose irbesartan1
Among patients with baseline UPCR of ≥3.0 g/g, serious TEAEs were experienced by 35% (34/97) of patients with sparsentan and 53% (50/94) of patients with maximum-labeled dose irbesartan1
Conclusions
- In the Phase 3 DUPLEX Study, patients with FSGS experienced rapid and sustained reductions in proteinuria with sparsentan vs. maximum-labeled dose irbesartan across baseline proteinuria subgroups1
- Irrespective of baseline proteinuria subgroup, patients reached low proteinuria thresholds at any time more often with sparsentan compared to maximum-labeled dose irbesartan1
- Sparsentan was generally well tolerated over 108 weeks of treatment across baseline proteinuria subgroups1
Related Content
Footnotes
*The DUPLEX Study was conducted during the COVID-19 pandemic.1 †Abnormal liver function tests met the following criteria: (1) new elevation in ALT or AST >3 × ULN with or without elevation of total serum bilirubin >2 × ULN; (2) 2-fold increase in ALT or AST above the baseline value in patients who had elevated values prior to taking study medication.1
ACEi, angiotensin-converting enzyme inhibitor; ALT, alanine aminotransferase; ARB, angiotensin II receptor blocker; AST, aspartate aminotransferase; BL, baseline; CI, confidence interval; COVID-19, coronavirus disease of 2019; CR, complete remission; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration ratio; FSGS, focal segmental glomerulosclerosis; GMR, geometric mean ratio; IST, immunosuppressive therapy; LS, least squares; RASi, renin-angiotensin-system inhibitor; RR, relative risk; SE, standard error; SOC, standard of care; TEAE, treatment-emergent adverse effect; ULN, upper limit of normal; UPCR, urine protein-to-creatinine ratio.
- Radhakrishnan J et al. Poster presented at: National Kidney Foundation Spring Clinical Meetings 2026; May 6-10, 2026; New Orleans, LA, USA. LB-23.
- Smith AR. Presented at: American Society of Nephrology Kidney Week 2024. October 24-27, 2024. San Diego, CA.
- Rheault MN et al. N Engl J Med. 2023;389:2436-2445.
- Kohan DE et al. Clin Sci (Lond). 2024;138(11):645-662.
- Trachtman H et al. Expert Rev Clin Immunol. 2024;20(6):571-576.
- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc.
MA-SP-26-0071 | June 2026