Sparsentan. Dual angiotensin II AT1 receptor blocker and endothelin ETA receptor antagonist, Treatment of focal segmental glomerulosclerosis, Treatment of IgA nephropathy
Abstract
Treatment of glomerular diseases remains challenging. There are limited therapeutic options currently available for focal segmental glomerulosclerosis (FSGS) and immunoglobulin A nephropathy (IgAN) and they are generally ineffective in a substantial proportion of patients who progress to end-stage kidney disease during long-term follow-up.
Standard management involving renin-angiotensin-aldosterone system (RAAS) inhibitors, corticosteroids and various immunosuppressive therapies does not always achieve sustained, complete or partial remission for most patients while causing serious or intolerable adverse effects. There is a substantial unmet need for new treatments to improve outcomes.
Sparsentan, a first-in-class, orally active compound combining angiotensin II type 1 (AT1) receptor blockade with endothelin ETA receptor antagonism, offers an innovative dual mechanism of action approach to the treatment of these diseases with a potentially greater nephroprotective effect, compared to RAAS or endothelin inhibition alone. We summarize the molecular and pharmacological features of sparsentan and discuss ongoing clinical trials in FSGS and IgAN.
These trials were designed to examine the long-term antiproteinuric effect, nephroprotective potential and safety profile of sparsentan. We also highlight new efforts to evaluate sparsentan in the treatment of Alport syndrome.
This review aims to elucidate the potential role of this novel agent in the management of glomerular diseases.