Sparsentan Shows Promise for Patients with Genetic Focal Segmental Glomerulosclerosis (gFSGS)

A recent analysis of the DUPLEX trial, the largest clinical trial to date for focal segmental glomerulosclerosis (FSGS), suggests that patients with genetic FSGS (gFSGS) may benefit significantly more from sparsentan treatment than those with other forms of FSGS.

The analysis, presented at the American Society of Nephrology’s Kidney Week 2024, reveals that patients with gFSGS experienced a more pronounced and sustained antiproteinuric response with sparsentan compared to irbesartan, the standard-of-care treatment.

“Our study analyzed a subset group of patients with genetic FSGS from the DUPLEX clinical trial,” explained principal investigator Jennifer Lai Yee, MD, PhD, MPH, of the Department of Pediatrics in the Division of Nephrology at the University of Michigan. “Consistent with the overall FSGS population in DUPLEX, our patients displayed more pronounced early and durable antiproteinuria effects with sparsentan compared to irbesartan, along with favorable outcomes in terms of complete remission or kidney composite kidney failure.”

The DUPLEX trial was a global, multicenter, randomized, double-blind, parallel-group, active-controlled study that compared sparsentan to irbesartan in 371 patients with FSGS. Patients were randomized in a 1:1 ratio to receive either sparsentan or irbesartan for 108 weeks.

While the original DUPLEX trial showed a greater reduction in proteinuria with sparsentan compared to irbesartan at 36 weeks, there were no statistically significant differences in eGFR slope at 108 weeks, the primary outcome measure. However, the posthoc analysis focusing on gFSGS patients reveals a more compelling picture.

The analysis identified 31 patients with gFSGS. These patients were younger and had a higher eGFR at baseline compared to the overall DUPLEX population, with most experiencing nephrotic-range proteinuria.

Results showed that sparsentan was associated with a faster and more pronounced reduction in proteinuria compared to irbesartan, with this effect lasting throughout the treatment period. Similar trends were observed in patients with NPHS2 mutations.

Importantly, complete remission was achieved by only one patient with gFSGS in the sparsentan group compared to none in the irbesartan group. Additionally, only one patient in the sparsentan group reached end-stage kidney disease compared to three in the irbesartan group.

“As the largest clinical trial for patients with genetic FSGS to date, our findings suggest that sparsentan can provide meaningful benefits for this historically treatment-resistant patient population,” concluded Dr. Lai Yee.

References:

1. Lai Yee J, Gong W, Inrig JK, et al. Outcomes of the DUPLEX Trial in Patients with Genetic Focal Segmental Glomerulosclerosis (gFSGS). Presented at American Society of Nephrology Kidney Week 2024. San Diego, CA. October 23-27, 2024.
2. Rheault MN, Alpers CE, Barratt J, et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023;389(26):2436-2445. doi:10.1056/NEJMoa2308550
3. Trachtman H, Radhakrishnan J, Rheault MN, et al. Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study. Kidney Int Rep. 2024;9(4):1020-1030. Published 2024 Jan 28. doi:10.1016/j.ekir.2024.01.032

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