SPARSENTAN

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

Sparsentan is a novel small-molecule candidate in Phase 3 development for the treatment of IgA nephropathy (IgAN). IgAN, also called Berger’s disease, is a type of glomerulonephritis. The disease causes inflammation and scarring of the glomeruli, leading to blood and protein leaking into the urine. Over time, IgAN can progress to end-stage kidney disease (ESKD). Learn more about IgAN.

MECHANISM OF ACTION

Sparsentan is a single molecule designed to selectively block the receptors of two pathways which are associated with kidney disease progression. The receptors are endothelin 1A and angiotensin II type 1.1

Endothelin I and angiotensin II have a role in kidney function decline by contributing to inflammation and fibrosis in the kidney, changes to the shape of podocytes, podocyte loss, and increased permeability of the glomerular filtration barrier.2 Endothelin I and angiotensin II are also vasoconstrictive, meaning they cause a narrowing of blood vessels and an increase in pressure in the glomeruli.

The goal of the sparsentan program for IgAN 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 IgAN.

PATIENT NEED

Globally, IgAN is the most common type of primary glomerulonephritis and often slowly progresses to end-stage kidney disease. IgAN 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

CLINICAL TRIAL

The PROTECT Study

In 2018, Travere Therapeutics initiated the PROTECT Study, a global pivotal Phase 3 clinical trial evaluating the safety and efficacy of sparsentan in patients with IgAN. 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. Top-line efficacy data from the 36-week interim efficacy endpoint are expected in the third quarter of 2021.


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.

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