Sparsentan

Sparsentan, the first-in-class dual antagonist of the endothelin type A receptor (ETAR) and the angiotensin II type 1 receptor (AT1R), exhibits comparable affinities for both receptors (9.3 nM for ETAR and 0.8 nM for AT1R).

It is orally active and was developed by combining the structural components of irbesartan, an AT1R antagonist, and biphenylsulfonamide, an ETAR antagonist. Initially intended for the treatment of hypertension, sparsentan has demonstrated efficacy in reducing proteinuria in patients with primary immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS).

The FDA granted accelerated approval in February 2023 based on the reduction of proteinuria in adults with IgAN at risk of rapid disease progression. Subsequently, in September 2024, sparsentan received full approval for an expanded indication.