Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis
New England Journal of Medicine – 2023
Sparsentan Versus Irbesartan in Pediatric Patients With FSGS
Journal article
Published on April 22, 2026
Contributors:
Rheault MN, Dell KM, Lieberman KV et al.
Rheault MN, Dell KM, Lieberman KV et al.
DOI:
10.1016/j.ekir.2026.106566
10.1016/j.ekir.2026.106566
Summary
Background
- Focal segmental glomerulosclerosis (FSGS) is a rare, progressive kidney condition characterized by a histological pattern of glomerular and podocyte injury.1-3 It is a leading cause of kidney failure in children worldwide1,4
- 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-creatinine ratio (UPCR) thresholds is associated with a lower risk of kidney failure1,6
- In the Phase 3 DUPLEX trial, treatment with sparsentan led to rapid and sustained reductions in proteinuria vs. maximum-labeled dose irbesartan, with a comparable safety profile1,7
- Sparsentan is a non-immunosuppressive, Dual Endothelin Angiotensin Receptor Antagonist (DEARA) indicated to reduce proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome1,8,9
- 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 edema9
Aim
The aim of this post hoc analysis of the Phase 3 DUPLEX trial was to evaluate efficacy and safety of sparsentan vs. maximum-labeled dose irbesartan in the pediatric subgroup (8 to <18 years) of patients with FSGS1
This post hoc exploratory analysis assessed:
- Percentage change from baseline in UPCR
- Achievement of the following:
- Complete remission of proteinuria (defined as UPCR <0.3 g/g)
- FSGS partial remission endpoint (defined as UPCR ≤1.5 g/g and >40% reduction from baseline)
- UPCR thresholds of <0.3 g/g, <0.5 g/g, <0.7 g/g, <1.0 g/g, or FSGS partial remission endpoint at any time during the double-blind period
- Rates of kidney failure* and a composite kidney endpoint†
- Safety outcomes: TEAEs
Figure. DUPLEX is a Phase 3, randomized, double-blind trial evaluating the efficacy and safety of sparsentan vs. active control, maximum-labeled dose irbesartan in adults and children (aged ≥8 years) with FSGS
Key findings
As early as 6 weeks, patients receiving sparsentan demonstrated a numerically greater reduction in proteinuria compared with those receiving maximum-labeled dose irbesartan.1 This reduction was sustained throughout the treatment period1
A numerically greater proportion of patients achieved complete remission of proteinuria (<0.3 g/g) at any time with sparsentan vs. irbesartan.1 Similar findings were observed across low proteinuria thresholds <0.5 g/g, <0.7 g/g, and <1.0 g/g, as well as the FSGS partial remission endpoint (UPCR ≤1.5 g/g and >40% reduction from baseline)1
Fewer patients receiving sparsentan progressed to kidney failure* or the composite kidney endpoint,† compared with those receiving maximum-labeled dose irbesartan1
In total, 15/16 patients (94%) received the target sparsentan dose.1 Sparsentan was well tolerated at doses up to 800 mg/d, with a safety profile similar to maximum-labeled dose irbesartan1
The most common treatment-emergent adverse events (TEAEs) included COVID-19,‡ dizziness, diarrhea, pyrexia, increased blood creatinine, and anemia1
• TEAEs of hyperkalemia occurred in 2 patients each in the sparsentan (13%) and irbesartan (11%) arms, and TEAEs of hypotension occurred in 3 patients (19%) in the sparsentan arm and in 1 patient (5%) in the irbesartan arm; none of these events were serious1
There were no TEAEs of acute kidney injury or TEAEs that led to treatment discontinuation in patients treated with sparsentan1
Conclusions
In this post hoc analysis of the Phase 3 DUPLEX Study, rapid and sustained reductions in UPCR were observed in pediatric patients with FSGS who received sparsentan compared with maximum-labeled dose irbesartan1
More patients achieved low proteinuria thresholds with sparsentan vs. maximum-labeled dose irbesartan1
Additionally, patients on sparsentan experienced fewer kidney failure events vs. maximum-labeled dose irbesartan1
Sparsentan was well tolerated up to doses of 800 mg/d with an overall safety profile similar to that of maximum-labeled dose irbesartan and was consistent across both the overall study population and the broad clinical trial experience1
Resources
Highlights from the DUPLEX pediatric subgroup
Related Content
Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis
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Sparsentan Clinical Trials in Glomerular Diseases: Defining Endpoints and a Path Forward in Light of the PARASOL Initiative
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Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated FSGS Enrolled in the DUPLEX Trial
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Footnotes
This study was supported by Travere Therapeutics, Inc. Please see the publication for the full list of disclosures.
*Defined as eGFR <15 mL/min/1.73m2 or kidney replacement therapy.
†Defined as confirmed 40% reduction in eGFR, kidney failure, or death.
‡Study was conducted during the COVID-19 pandemic.
COVID-19, coronavirus disease 2019; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; RASi, renin-angiotensin system inhibitor; SOC, standard of care; TEAE, treatment-emergent adverse event; UPCR, urine protein-creatinine ratio.
- Rheault MN et al. Kidney Int Rep. 2026;106566.
- Shabaka A et al. Nephron. 2020;144:413-427.
- Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100:S1-S276.
- Gipson DS et al. JAMA Netw Open. 2022;5(8):e2228701.
- Boussetta A et al. Tunis Med. 2023;101(3):373-378.
- D’Agati VD et al. N Engl J Med. 2011;365:2398-2411.
- Rheault MN et al. N Engl J Med. 2023;389:2436-2445.
- Kohan DE et al. Clin Sci (Lond). 2024;138(11):645-662.
- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc.
MA-SP-26-0078 | July 2026