Sparsentan as an investigational therapeutic candidate for the treatment of IgA nephropathy

Sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), is a novel investigational product candidate in Phase 3 development for the treatment of IgA nephropathy (IgAN). IgA nephropathy, also called Berger’s disease, is a rare kidney disorder characterized by the buildup of immunoglobulin A (IgA), a protein that helps the body fight infections, in the kidneys. The deposits of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to blood in the urine (hematuria), and protein in the urine (proteinuria). Other symptoms of IgA nephropathy may include kidney pain, swelling (edema) and high blood pressure. Over time, IgAN can progress to end-stage kidney disease (ESKD). Learn more about IgAN.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted sparsentan orphan drug designation for IgAN.


Sparsentan is a single molecule designed to selectively block the receptors of two pathways that are associated with kidney disease progression. The receptors are endothelin 1A and angiotensin II type 1.1 The endothelin-1 (ET-1) & angiotensin II (Ang II) signaling pathways play fundamental roles in disease pathophysiology and progression in several kidney diseases, including IgA nephropathy. 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 The goal of the sparsentan program for IgA nephropathy 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 IgA nephropathy.


Globally, IgA nephropathy is the most common type of primary glomerulonephritis and often progresses to end-stage kidney disease. IgA nephropathy frequently occurs in adolescence or early adulthood, usually in the second and third decades of life.3 Disease progression to kidney failure can be slow and varies among populations, with long-term follow-up showing that 25% of high-risk patients with IgAN develop end-stage kidney disease within 10 years.4,5



In 2018, Travere Therapeutics initiated the PROTECT Study, a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of sparsentan in patients with IgA nephropathy. Patients are randomized to receive either sparsentan or irbesartan, the active control. The primary efficacy endpoint is the change in proteinuria (urine protein-to-creatinine ratio) at Week 36 from baseline. Secondary efficacy endpoints include the rate of change in eGFR from the initiation of randomized treatment over 58-week and 110-week periods, as well as the rate of change in eGFR over 52-week and 104-week periods following the first six weeks of randomized treatment.

In August of 2021, Travere reported that the ongoing PROTECT Study of sparsentan in IgA nephropathy met its pre-specified interim primary efficacy endpoint with statistical significance demonstrating a greater than threefold reduction of proteinuria from baseline after 36 weeks of treatment, compared to the active control irbestartan (p<0.0001). Per study protocol, patients will continue in a blinded manner in the PROTECT Study to fully assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis. Topline results from the confirmatory endpoint analysis are expected in the second half of 2023.


  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. Barratt and Feehally. J Am Soc Nephrol. 2005;16:2088-2097.
  4. Xie, et al. PLoS One. 2012;7:e38904.
  5. Donadio and Grande. N Engl J Med. 2002;347:738-748.