Sparsentan is an investigational therapeutic candidate for the treatment of focal segmental glomerulosclerosis

Sparsentan is a novel small-molecule candidate in Phase 3 development for the treatment of focal segmental glomerulosclerosis (FSGS). FSGS is a pattern of damage to the glomeruli (filter units) of the kidney with numerous causes that often leads to decline in kidney function and progression to kidney failure. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted sparsentan orphan drug designation for FSGS.


Learn more about FSGS


Mechanism of Action

Sparsentan is a novel investigational product candidate selectively targeting the endothelin A receptor (ETAR) and the angiotensin II subtype 1 receptor (AT1R).1 Pre-clinical data have shown that blockade of both endothelin type A and angiotensin II type 1 pathways in forms of rare chronic kidney disease, reduces proteinuria, protects podocytes and prevents glomerulosclerosis and mesangial cell proliferation.2

Proteinuria is a standard measure of disease activity, and a predictor of and contributor to disease progression in FSGS.3,4

The goal of the sparsentan program for FSGS is to develop a well-tolerated, safe and effective treatment that sustainably reduces proteinuria and protects the long-term health of kidneys in people living with FSGS.


Patient Need

FSGS can be characterized by an aggressive clinical course. 50% of patients with nephrotic-range proteinuria who do not reach remission or partial remission will require kidney transplant or dialysis within 5-10 years of diagnosis.5

Patients who are steroid resistant are at a significantly higher risk of disease progression and kidney failure.5,6 For those with primary FSGS (not secondary to another condition) who undergo kidney transplantation, FSGS recurs in the transplanted kidney in approximately one-third of patients.7

Clinical Trials

The DUPLEX Study

The DUPLEX Study is the largest interventional study to date in FSGS. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled Phase 3 clinical trial assessing the efficacy and safety of sparsentan in 371 patients ages 8 to 75 years with primary FSGS. After a two-week washout period, patients are randomized 1:1 to receive either sparsentan or irbesartan, the active control, and subsequently dose titrated to the maximum dose of 800 mg of sparsentan or 300 mg of irbesartan, as tolerated. In February 2021, the Company announced that the pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its pre-specified interim FSGS partial remission of proteinuria (FPRE) endpoint with statistical significance. FPRE is a clinically meaningful endpoint defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 g/g and a >40 percent reduction in UP/C from baseline. After 36 weeks of treatment, 42.0 percent of patients receiving sparsentan achieved FPRE, compared to 26.0 percent of irbesartan-treated patients (p=0.0094). The study’s primary efficacy endpoint in the U.S. is the eGFR total slope from day 1 to week 108 of treatment. The primary efficacy endpoint in Europe is the eGFR chronic slope, from week 6 to week 108 of treatment, following the initial acute effect of randomized treatment. In May 2023, the Company announced topline primary efficacy results from the DUPLEX Study of sparsentan in FSGS. The DUPLEX Study did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment. Secondary and topline exploratory endpoints trended favorably for sparsentan. Treatment with sparsentan resulted in a reduction of proteinuria that was sustained through 108 weeks of treatment. Results from the two-year analysis demonstrated that sparsentan was well-tolerated and has shown a comparable safety profile to irbesartan. Patients who completed the DUPLEX double-blind portion of the study on treatment were eligible to participate in the open-label extension of the trial. In December 2023, the Company announced that following its engagement with the FDA on the two-year results from the DUPLEX Study, the Company is conducting additional analyses of FSGS data, and plans to re-engage with the FDA later in 2024 following the Company’s consideration of additional evidence. Read the press release>



1. Trachtman, et al. J Am Soc Nephrol. 2018;29:2745-2754.
2. Komers and Plotkin. Am J Physiol Regul Integr Comp Physiol. 2016;310:R877-R884.
3. Abbate M, et al. Am J Pathol 2002; 161:2179–2193.
4. Abbate M, et al. J Am Soc Nephrol 2006; 17:2974–2984.
5. Korbet. J Am Soc Nephrol. 2012;23:1769-1776.
6. KDIGO Clinical Practice Guideline on Glomerular Diseases, published in the October 2021 issue of Supplements to Kidney International.
7. Uffing, et al. Clin J Am Soc Nephrol. 2020;15:247-256.