Overview
Sparsentan is a dual antagonist of the endothelin type A receptor (ETR) and the angiotensin II (Ang II) type 1 receptor (ATR) with a similar affinity for both (9.3 nM for ETR and 0.8 nM for ATR). Sparsentan is first in its class and orally active, and was created by merging the structural elements of irbesartan, an ATR antagonist, and biphenylsulfonamide, an ETR antagonist. In February 2023, the use of sparsentan to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression was approved by the FDA under accelerated approval based on reduction of proteinuria. Sparsentan was initially developed for the treatment of hypertension; however, it has shown to be efficient in the reduction of proteinuria in patients with IgAN and focal segmental glomerulosclerosis (FSGS). Compared to irbesartan, sparsentan reduces proteinuria to a greater extent. Furthermore, it is the first non-immunosuppressive therapy for the reduction of proteinuria in IgAN. The use of sparsentan may cause hepatotoxicity and embryo-fetal toxicity.
Background
Sparsentan is a dual antagonist of the endothelin type A receptor (ETR) and the angiotensin II (Ang II) type 1 receptor (ATR) with a similar affinity for both (9.3 nM for ETR and 0.8 nM for ATR). Sparsentan is first in its class and orally active, and was created by merging the structural elements of irbesartan, an ATR antagonist, and biphenylsulfonamide, an ETR antagonist. In February 2023, the use of sparsentan to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression was approved by the FDA under accelerated approval based on reduction of proteinuria. Sparsentan was initially developed for the treatment of hypertension; however, it has shown to be efficient in the reduction of proteinuria in patients with IgAN and focal segmental glomerulosclerosis (FSGS). Compared to irbesartan, sparsentan reduces proteinuria to a greater extent. Furthermore, it is the first non-immunosuppressive therapy for the reduction of proteinuria in IgAN. The use of sparsentan may cause hepatotoxicity and embryo-fetal toxicity.
Indication
Sparsentan is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.
Associated Conditions
- Proteinuria
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