Search for information about a product,
therapeutic area or event

Search

Media, investors, advocacy organizations and others, please contact us here.

Hero Section Background Image

Antiproteinuric Effect of Sparsentan After Maximized Irbesartan in Patients With Focal Segmental Glomerulosclerosis (FSGS) in the DUPLEX Open-Label Extension (OLE)

Poster
Published on May 6, 2026

Topics:

Nephrology FSGS DUPLEX Clinical
Contributors
Coppock G, Kirsztajn GM,
 Inrig J et al.


Presented at:
NKF SCM 2026


View poster
Share:

About the research

View Download

Summary

Background

  • Focal segmental glomerulosclerosis (FSGS) is associated with a substantial risk of progressing to kidney failure within 10 years of diagnosis1,2
  • Lowering proteinuria across a range of urine protein-to-creatinine (UPCR) thresholds is associated with a reduced risk of kidney failure1,3
  • 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 similar safety profile1,4
  • Sparsentan is a non-immunosuppressive, Dual Endothelin Angiotensin Receptor Antagonist indicated to reduce proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome1,5-7
    • 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 edema7


Aim

The aim of this analysis of the Phase 3 DUPLEX trial was to report the efficacy and safety of sparsentan in patients with FSGS who received maximum-labeled dose irbesartan in the double-blind period and then initiated sparsentan in the open-label extension (OLE) period1

Figure. DUPLEX study design1

This analysis evaluated outcomes through the 108-week double-blind period and during the 156-week OLE period (data cutoff August 1, 2025) in patients who received maximum-labeled dose irbesartan during the double-blind period and then initiated sparsentan in the OLE period1

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

Patients who were receiving 800 mg/d sparsentan or 300 mg/d irbesartan at the end of the double-blind period were titrated to the target dose of 800 mg/d sparsentan after 2 weeks of 400 mg/d sparsentan in the OLE. Patients who were receiving 400 mg/d sparsentan or 150 mg/d irbesartan at the end of the double-blind period were titrated to the target dose of 400 mg/d sparsentan after 2 weeks of 200 mg/d sparsentan in the OLE. Patients who were receiving 200 mg/d sparsentan or 75 mg/d irbesartan at the end of the double-blind period received the target dose of 200 mg/d sparsentan throughout the OLE1

Key findings

Of 187 patients who received maximum-labeled dose irbesartan during the double-blind period, 114 entered the OLE and received sparsentan1

After switching from maximum-labeled dose irbesartan to sparsentan, reductions in proteinuria were observed and sustained throughout the OLE period1

Figure. Change in UPCR by visit in the double-blind and OLE periods1*

Mean UPCR by visit (standard error [SE]), g/g (patients who switched to sparsentan):

  • Week 0: 2.0 g/g (SE: 1.80-2.26)
  • Week 48: 1.1 g/g (SE: 0.98-1.27)
  • Week 96: 0.8 g/g (SE: 0.72-1.00)
  • Week 156: 0.9 g/g (SE: 0.70-1.17)

OLE Week 0 reflects the Week 112 visit for evaluable patients who entered the OLE period1

Across UPCR thresholds (UPCR <0.3 g/g, <0.7 g/g, and <1.5 g/g), the proportion of patients who achieved low proteinuria increased from the double-blind period through the OLE among those who received maximum-labeled dose irbesartan during the double-blind period and then initiated sparsentan in the OLE1

  • Approximately 29% achieved complete remission of proteinuria (<0.3 g/g) at any time during the OLE period. Of the 33 patients who achieved complete remission, over 60% (20/33 patients) did so for the first time following the switch to sparsentan1
  • Approximately 54% achieved UPCR <0.7 g/g at any time during the OLE period. Of the 61 patients who achieved UPCR <0.7 g/g, over 40% (26/61 patients) did so for the first time following the switch to sparsentan1

Figure. Proportion of patients who achieved low proteinuria

A greater proportion of patients who switched from maximum-dose irbesartan to sparsentan in the OLE achieved low proteinuria levels compared to their time on irbesartan in the double-blind period1

Achievement of low proteinuria thresholds at any time during the double-blind period (patients randomized to maximum-labeled dose irbesartan)1:

  • <0.3 g/g: 7.5% (14/187) of patients
  • <0.7 g/g: 22.5% (42/187) of patients
  • <1.5 g/g: 50.8% (95/187) of patients

Achievement of low proteinuria thresholds at any time through the OLE (patients who switched to sparsentan)1:

  • <0.3 g/g: 28.9% (33/114) of patients
  • <0.7 g/g: 53.5% (61/114) of patients
  • <1.5 g/g: 74.6% (85/114) of patients

Sparsentan was well-tolerated, with the most common treatment emergent adverse events (TEAEs) broadly consistent with those reported in the double-blind period1,4

The most common TEAEs (≥10% of patients) included1:

  • COVID-19‡
  • Hyperkalemia
  • Hypotension
  • Upper respiratory tract infection
  • Headache
  • Influenza
  • Anemia

Table. Overview of TEAEs1

Over 90% of patients who switched from maximum-labeled dose irbesartan in the double-blind period to sparsentan during the OLE experienced a TEAE1

Achievement of low proteinuria thresholds at any time during the double-blind period (patients randomized to maximum-labeled dose irbesartan)1:

  • <0.3 g/g: 7.5% (14/187) of patients
  • <0.7 g/g: 22.5% (42/187) of patients
  • <1.5 g/g: 50.8% (95/187) of patients

Achievement of low proteinuria thresholds at any time through the OLE (patients who switched to sparsentan)1:

  • <0.3 g/g: 28.9% (33/114) of patients
  • <0.7 g/g: 53.5% (61/114) of patients
  • <1.5 g/g: 74.6% (85/114) of patients

Among patients who switched from maximum-labeled dose irbesartan in the double-blind period to sparsentan during the OLE, patients experienced1:

  • Serious TEAEs: 36% (41/114) of patients
  • TEAEs leading to treatment discontinuation: 15% (17/114) of patients

None of the 3 deaths resulting from TEAEs were considered treatment-related1

Conclusion

  • In the Phase 3 DUPLEX study, patients who switched to sparsentan in the OLE after receiving maximum-labeled dose irbesartan for 108 weeks experienced rapid and sustained reductions in proteinuria1
  • A greater proportion of enrolled patients in the OLE achieved low proteinuria thresholds, including complete remission of proteinuria (<0.3 g/g) and UPCR <0.7 g/g, compared with the double-blind period1
  • Sparsentan was generally well tolerated, with no new safety signals1

Related Content

Visual abstract NephrologyFSGS

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)

National Kidney Foundation (NKF) Spring Clinical Meetings – 2025

Learn more
Poster NephrologyFSGS

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

Learn more
Presentation NephrologyFSGS

Patients With Focal Segmental Glomerulosclerosis (FSGS) Achieved Low Proteinuria Targets Earlier and More Often With Sparsentan (SPAR) vs Irbesartan (IRB) in DUPLEX

62nd European Renal Association (ERA) Congress – 2025

Learn more
Footnotes

*Abnormal liver function test was defined as new elevation in ALT or AST >3 ×ULN (with or without elevation of total serum bilirubin to >2 ×ULN) or 2-fold increase in ALT or AST above the baseline value in a patient who had elevated values prior to starting study medication.1 ‡The DUPLEX Study was conducted during the COVID-19 pandemic.1

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; COVID-19, coronavirus disease of 2019; CR, complete remission; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; OLE, open-label extension; RASi, renin-angiotensin-system inhibitor; SE, standard error; SOC, standard of care; 
TEAE, treatment-emergent adverse event; UPCR, urine protein-to-creatinine ratio.

  1. Coppock G et al. Poster presented at: National Kidney Foundation Spring Clinical Meetings 2026; May 6-10, 2026; New Orleans, LA, USA. G-434.
  2. Pitcher D, et al. J Am Soc Nephrol. 2025;36(7):1398-1413.
  3. Smith AR. Presented at: American Society of Nephrology Kidney Week 2024. October 24-27, 2024. San Diego, CA.
  4. Rheault MN, et al. N Engl J Med. 2023;389:2436-2445.
  5. Kohan DE et al. Clin Sci (Lond). 2024;138(11):645-662.
  6. Trachtman H, et al. Expert Rev Clin Immunol. 2024;20(6):571-576.
  7. FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc.


MA-SP-26-0076 | June 2026