Long-term nephroprotective effects of sparsentan in FSGS

Data from a post hoc analysis of the DUET study supports the long-term (240 weeks) nephroprotective potential and safety of sparsentan in focal segmental glomerulosclerosis (FSGS). Sustained proteinuria reduction was observed in patients who continued sparsentan treatment without any new or unexpected treatment-emergent adverse events (TEAEs) observed with treatment with sparsentan [1].

Sparsentan is a dual endothelin angiotensin receptor antagonist, a novel investigational molecule that selectively targets the endothelin A receptor and the angiotensin II subtype 1 receptor. In forms of rare chronic kidney disease, blockade of both endothelin type A and angiotensin II type 1 pathways has shown to be able to reduce proteinuria, protect podocytes, and prevent glomerulosclerosis and mesangial cell proliferation. The 8-week, double-blind period of the phase 2 DUET trial (NCT01613118) in patients with FSGS (excluding secondary FSGS), sparsentan (200, 400, and 800 mg/day) resulted in greater proteinuria reduction versus irbesartan 300 mg/day. Dr Tarak Srivastava (Children’s Mercy Hospital, USA) presented the 240-week analysis of the DUET open-label extension (OLE) study which assessed the on-treatment long-term efficacy and safety of sparsentan. A total of 108 patients who received ≥1 sparsentan dose were examined from the first sparsentan dose (double-blind or OLE) for 240 weeks (4.6 years). Outcomes examined in the 240-week analysis included proteinuria, estimated glomerular filtration rate, blood pressure, and most common TEAES. According to Dr Srivastava, 43% of patients experienced ≥1 complete remission of proteinuria at any time. “The chronic slope estimate all on-treatment data is −4.16 (95% CI −5.8 to −2.5) mL/min/1.73m². There was also a sustained reduction in blood pressure of between 8 and 10 units in systolic blood pressure and 6 and 8 units in diastolic pressure.” The most common TEAEs are outlined below (see Table).

Table: Most common treatment-related adverse events



Dr Srivastava mentioned that the ongoing phase 3 DUPLEX study (NCT03493685) is evaluating the long-term antiproteinuric efficacy and safety of sparsentan in FSGS over a double-blind period of 112 weeks followed by an OLE of 156 weeks.

1. Srivastava T, et al. Long-Term Efficacy and Safety of Sparsentan in FSGS: 240-Week Analysis of the DUET Open-Label Extension (OLE). FR-OR57, ASN Kidney Week 2022, 3–6 Nov.

 

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Posted on 8 December 20228 December 2022