SPARSENTAN FOR IGAN

Sparsentan is 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, IgA nephropathy can progress to end-stage kidney disease (ESKD). The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted sparsentan orphan drug designation for IgA nephropathy.

 

Learn more about IgAN

Mechanism of Action

Sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), 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

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.

 

Patient Need

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 IgA nephropathy develop end-stage kidney disease within 10 years.4,5

Clinical Trial

The PROTECT Study

Initiated by Travere Therapeutics in 2018, the ongoing PROTECT Study is one of the largest interventional studies to date in IgA nephropathy. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of sparsentan, compared to 300mg of irbesartan, in 404 patients ages 18 years and up with IgA nephropathy and persistent proteinuria despite available ACE or ARB therapy.

In August 2021, Travere announced the PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance. After 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8 percent, compared to a mean reduction in proteinuria from baseline of 15.1 percent for irbesartan-treated patients (p<0.0001). The company believes that preliminary eGFR data available at the time of the interim analysis are indicative of a potential clinically meaningful treatment effect after two years of treatment. Preliminary results at the time of the interim assessment suggested that sparsentan had been generally well-tolerated to date in the study and consistent with its overall observed safety profile.

The PROTECT Study is fully enrolled and is scheduled to continue as planned on a blinded basis to 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.

Read the recent regulatory update

Sources
  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.