Advancing Care in FSGS: A New Era in Treatment and Clinical Understanding
In this issue we:
- Describe the unmet need and disease burden associated with focal segmental glomerulosclerosis (FSGS)
- Announce the US FDA approval of sparsentan to reduce proteinuria in adult and pediatric patients ≥8 years of age with FSGS without nephrotic syndrome
- Define nephrotic syndrome and nephrotic-range proteinuria
- Review safety and efficacy data from the Phase 3 DUPLEX Study that supported the regulatory approval of sparsentan for FSGS
FSGS is associated with elevated proteinuria and poor long-term kidney outcomes1-3
FSGS is a rare, progressive kidney condition characterized by a histological pattern of podocyte and glomerular injury that results in a variable degree of proteinuria.1,2
Proteinuria is a central marker of activity in FSGS, with elevated levels associated with an increased risk of progression to kidney failure.1,2 FSGS, although considered a rare condition, is one of the most common causes of kidney failure, affecting both adult and pediatric populations.4-6
Findings from PARASOL suggest that proteinuria reduction is an outcome closely associated with long-term kidney prognosis.7 These data support the use of proteinuria reduction as a clinical trial endpoint.
Endothelin & Proteinuria in Glomerular Pathophysiology
Hear Drs Donald Kohan and Yelena Drexler discuss the role of endothelin and proteinuria in glomerular diseases.
US FDA approval of sparsentan provides a new option for many patients with FSGS8,9
Sparsentan is a non-immunosuppressive, single-molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA) that directly targets podocyte injury by blocking the endothelin and angiotensin pathways in tandem.10,11
In April 2026, sparsentan became the first FDA-approved medicine for reducing proteinuria in adult and pediatric patients aged ≥8 years with FSGS without nephrotic syndrome.8,9
Nephrotic syndrome is defined by the presence of three concurrent criteria: nephrotic-range 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 edema.8
Importantly, nephrotic syndrome is a clinical state where one or more of the defining criteria may change or improve in response to treatment.12 Furthermore, patients may experience nephrotic-range proteinuria without co-occurrence of hypoalbuminemia and edema.12
How Does Nephrotic-Range Proteinuria Differ From Nephrotic Syndrome in Focal Segmental Glomerulosclerosis (FSGS)?
Learn more about the distinction between nephrotic-range proteinuria and nephrotic syndrome.
Clinical data supported approval of sparsentan for reducing proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome13
DUPLEX is one of the largest global, randomized, double-blind, active-controlled Phase 3 FSGS clinical trials to date.13 The study assessed the safety and efficacy of sparsentan in pediatric and adult patients with biopsy-proven FSGS or documented genetic mutation in podocyte protein associated with FSGS, compared with maximum-labeled dose irbesartan.13
DUPLEX study design13
Data from DUPLEX demonstrated that in the overall patient cohort, patients treated with sparsentan had greater reductions in proteinuria compared with irbesartan from baseline to Week 108 (50% vs. 32%).13
Overall patient cohort: Change in UPCR from baseline up to Week 10813
Fewer patients also progressed to kidney failure with sparsentan vs. irbesartan in the overall patient cohort13
Overall patient cohort: Proportion of patients who reached kidney failure13
Sparsentan Versus Irbesartan in Focal Segmental Glomerulosclerosis
Explore results from the Phase 3 DUPLEX Study evaluating sparsentan vs. irbesartan in patients with FSGS.
Given the sparsentan mechanism of action and because key drivers of disease progression may differ according to nephrotic syndrome status, subgroup analyses were conducted within the overall DUPLEX study population.8,13
Relative reductions in proteinuria were observed with sparsentan versus irbesartan in the subgroup of patients without nephrotic syndrome (48% vs. 27%; difference 29% [95% CI, 9% to 44%]).8 Nephrotic syndrome was defined as (a) documentation of nephrotic syndrome in the medical history, or (b) the concurrent presence of proteinuria >3.5 g/24h (adults) or UPCR >2.0 g/g (pediatric patients <18 years of age), serum albumin <3.0 g/dL, and edema at baseline.13
Without nephrotic syndrome patient subgroup: Change in UPCR from baseline up to Week 1088
In the subgroup without nephrotic syndrome, fewer patients reached kidney failure with sparsentan compared to irbesartan.14
Without nephrotic syndrome patient subgroup: Proportion of patients who reached kidney failure14
In the overall patient cohort, sparsentan was generally well tolerated, with a safety profile comparable to irbesartan.8,13 The most common adverse events reported in 2% or more of patients with FSGS included peripheral edema, hypotension, hyperkalemia, dizziness, anemia, acute kidney injury, and transaminase elevations.8,13
Most common adverse events8
Sparsentan Clinical Trials in Focal Segmental Glomerulosclerosis (FSGS)
For access to more data from the Phase 3 DUPLEX trial, as well as additional analyses, visit our dedicated hub for sparsentan clinical trials in FSGS.
The evolving treatment landscape of FSGS
FSGS is a rare, progressive kidney condition associated with persistent proteinuria and an increased risk of progression to kidney failure, underscoring a need for safe and effective approaches to lower proteinuria.1,3,7 Clinical data from the Phase 3 DUPLEX trial demonstrated that treatment with sparsentan was well tolerated and led to greater and sustained reductions in proteinuria in the overall FSGS patient cohort, with similar findings observed in the subgroup of patients without nephrotic syndrome, compared with irbesartan.8,13
In this context, the approval of sparsentan represents an important expansion of treatment options for people living with FSGS without nephrotic syndrome and reflects continued progress in addressing unmet needs within the rare kidney disease community.9
Related Content
Exploring Clinical Trial Endpoints in FSGS: Spotlight on Proteinuria
Learn more about proteinuria as a primary clinical trial endpoint for focal segmental glomerulosclerosis studies.
FSGS in Focus: Drivers of Progression and the Patient Burden
Learn about FSGS pathophysiology, long-term outcomes, and the humanistic burden experienced by patients and their providers.
References
*Includes related terms.8 †Including orthostatic hypotension.8 ‡Elevations in ALT or AST greater than 3-fold ULN.8
- Tumlin J et al. Presented at: National Kidney Foundation Spring Clinical Meetings 2025; April 10-13, 2025; Boston, USA. LB-07.
- Shabaka A et al. Nephron. 2020;144(9):413-427.
- Pitcher D et al. Journal of the American Society of Nephrology. 2025;36(7):1398-1413.
- Go AS et al. J Am Soc Nephrol. 2021;32(9):2303-2314.
- Kitiyakara C et al. Am J Kidney Dis. 2004;44(5):815-825.
- D’Agati VD et al. N Engl J Med. 2011;365(25):2398-2411.
- Mariani L et al. Am J Kidney Dis. 2025;85(5):610-617.
- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc.
- Travere Therapeutics Announces Full FDA Approval of FILSPARI® (sparsentan), the First and Only Approved Medicine for FSGS. Updated April 14, 2026. Accessed April 14, 2026. https://ir.travere.com/press-releases/news-details/2026/Travere-Therapeutics-Announces-Full-FDA-Approval-of-FILSPARI-sparsentan-the-First-and-Only-Approved-Medicine-for-FSGS/default.aspx.
- Kohan DE et al. Clin Sci (Lond). 2024;138(11):645-662.
- Komers R et al. Am J Physiol Regul Integr Comp Physiol. 2016;310(10):R877-R884.
- Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100(4S):S1-S276.
- Rheault MN et al. N Engl J Med. 2023;389(26):2436-2445.
- Data on file. Travere Therapeutics, Inc.
MA-DS-26-0047 | May 2026