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Clinical benefits of sparsentan for patients with FSGS

Presented by
Prof. Michelle Rheault, University of Minnesota, MN, USA
ASN 2023
Phase 3, DUPLEX
In the largest study of focal segmental glomerulosclerosis (FSGS) ever conducted, sparsentan significantly reduced proteinuria compared with the active control irbesartan. The estimated glomerular flow rate (eGFR) was not changed.

Despite currently available treatments, patients with FSGS are likely to progress to kidney failure. “Patients with FSGS who have nephrotic-range proteinuria have an over 50% risk of reaching end-stage kidney disease within 5 to 10 years of their diagnosis,” Prof. Michelle Rheault (University of Minnesota, MN, USA) explained [1,2]. Sparsentan, a dual endothelin and angiotensin receptor antagonist, has previously been shown to reduce proteinuria in patients with FSGS in a phase 2 trial.

Prof. Rheault presented the results of the current phase 3, double-blind, active-controlled, global DUPLEX study (NCT03493685), which evaluated sparsentan compared with the angiotensin receptor blocker irbesartan. Inclusion criteria were a primary FSGS confirmed by biopsy or genetic testing, urinary protein creatine ratio (UPCR) ≥1.5 g/g, and eGFR ≥30 mL/min/1.73 m2. The participants were randomised 1:1 to sparsentan (n=184) or irbesartan (n=187) for 108 weeks. Sparsentan and irbesartan were started at 400 mg/day and 150 mg/day and were titrated to 800 mg/day and 300 mg/day, respectively. The primary endpoints were the slope of eGFR, depicting changes over the trial period, and the proportion of patients achieving UPCR ≤1.5 g/g, with a ≥40% reduction. The population was young, with a mean age for each group around 42 years.

The eGFR chronic slope from week 6 to week 108 was 0.9 (95% CI -1.27 to 3.04). No eGFR-related endpoints were statistically significant. At 108 weeks, 37.5% of the participants receiving sparsentan had achieved partial remission, compared with 22.6% of those taking irbesartan (RR 1.60; 95% CI 1.13–2.25). “Proteinuria decreased rapidly in both groups, with larger reductions seen in patients treated with sparsentan,” Prof. Rheault said. The sparsentan group was more likely to go into complete remission of proteinuria at any point during the trial (RR 2.47; 95% CI 1.37–4.45). Adverse events were comparable in both groups.

  1. Rheault MN, et al. Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with Focal Segmental Glomerulosclerosis (FSGS): Results from the Phase 3 DUPLEX Trial. FR-OR108, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.
  2. Rheault MN, et al. N Engl J Med 2023;Nov 3. DOI:1056/NEJMoa2308550.


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