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.
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.
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
The DUPLEX & DUET Studies
The Phase 3 DUPLEX Study is the largest interventional study to date in FSGS, and the only study in FSGS against a maximally dosed active comparator. While DUPLEX achieved its pre-specified interim FSGS partial remission of proteinuria (FPRE) endpoint with statistical significance at 36 weeks, it did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment. The two-year results from the study were published in the New England Journal of Medicine and showed that FILSPARI delivered clinically meaningful benefit at 108 weeks with significant proteinuria reduction, higher rates of partial and complete remission, and a lower rate of end-stage kidney disease compared to active control. The Phase 2 DUET Study of FILSPARI in FSGS met the primary efficacy endpoint for the combined treatment group, demonstrating a greater than two-fold reduction in proteinuria compared to irbesartan. FILSPARI was well-tolerated with a safety profile that was consistent across all clinical trials conducted to date and comparable to the maximally dosed active control, irbesartan, including no drug-induced liver injury and no fluid overload. Patients who completed the DUPLEX and DUET double-blind portions of the studies on treatment were eligible to participate in the open-label extension of the trials. In May 2025, Travere announced that the U.S. Food and Drug Administration had accepted the company’s supplemental New Drug Application (sNDA) for traditional approval of FILSPARI in FSGS, and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 13, 2026. 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.