Travere Therapeutics
Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) with high selectivity for the endothelin type A receptor (ETAR) and angiotensin II type 1 receptor (AT₁R).¹ ² In the Phase 3 PROTECT trial (a double-blind, randomized, active-controlled trial in adult patients [N=404] with IgA nephropathy), sparsentan demonstrated superior proteinuria reduction, better preservation of kidney function, and prolonged kidney survival compared with maximum labeled dose irbesartan.³ Treatment with sparsentan was well tolerated with a comparable safety profile to irbesartan.³
Data from post hoc and subgroup analyses of the PROTECT trial presented at ASN 2024 showed that achievement of low proteinuria was predictive of better long-term kidney function, with complete remission of proteinuria achieved earlier and more frequently with sparsentan vs irbesartan regardless of baseline proteinuria levels.⁴ ⁵ Safety data from these analyses continued to show a consistent safety profile for sparsentan.⁴ ⁵
At ASN 2024 and ERA 2025, data from the Phase 3 PROTECT open-label extension (OLE) and the Phase 2 SPARTACUS study (an open-label, single-arm multicenter trial in adult patients [N=48] with IgA nephropathy), respectively, suggested that concomitant use of sparsentan and a sodium-glucose cotransporter 2 inhibitor (SGLT2i) resulted in further reductions in proteinuria and was well tolerated with no new safety signals.⁶ ⁷ Specifically, data from the PROTECT OLE trial showed that the addition of an SGLT2i to stable sparsentan treatment improved proteinuria levels over 48 weeks.⁶ Similarly, data from the final analysis of the SPARTACUS trial indicated that switching from a renin-angiotensin system inhibitor (RASi) to sparsentan on a background of stable SGLT2i treatment led to rapid and sustained reductions in proteinuria and albuminuria over 24 weeks.⁷
Whether used alone or in combination with an SGLT2i, sparsentan has exhibited rapid and sustained proteinuria reduction, prolonged kidney survival, and a slowed rate of kidney function decline, demonstrating long-term nephroprotective effects.³ ⁶ ⁷ Sparsentan has shown a consistent safety profile across trials comparable to maximum labeled dose irbesartan and is well tolerated.³ ⁶ ⁷
Additionally, an analysis of patient-reported outcomes (PROs) from the PROTECT trial presented at ASN 2024 suggests that patients receiving sparsentan have a lower burden of kidney disease and generally trend toward a better health-related quality of life (HRQoL) compared with those receiving irbesartan.⁸ Studies have shown that improving clinical outcomes, such as reduction in proteinuria, may lessen the negative impact on quality of life in IgA nephropathy.⁹
References:
MA-SP-25-0130 | September 2025
The Phase 3 PROTECT Study evaluates long-term efficacy and safety of sparsentan versus irbesartan in IgA nephropathy
This analysis of the ongoing PROTECT OLE period evaluated the safety and efficacy of adding an SGLT2i to stable sparsentan in IgA nephropathy
