DUPLEX: Sparsentan Outperforms Irbesartan in Reaching Key Proteinuria Threshold in FSGS

New data from the phase 3 DUPLEX study has demonstrated that more participants with focal segmental glomerulosclerosis (FSGS) treated with sparsenten (Filspari) reached proteinuria levels below 0.7 g/g compared to those receiving irbesartan.1

These findings were presented at the American Society of Nephrology (ASN) Kidney Week 2025, held November 5-9, 2025, in Houston, Texas, by Jai Radhakrishnan, MD, Professor of Medicine and Director of Clinical Services of the Nephrology Division, Columbia University Medical Center.

“Sparsentan is a non-immunosuppressive dual endothelin angiotensin receptor antagonist (DEARA) that led to rapid and sustained proteinuria reduction vs maximum labeled dose irbesartan in patients with FSGS in the pivotal, phase 3 DUPLEX trial,” Radhakrishnan and colleagues wrote in their poster.1 “In large-scale analyses, the PARASOL initiative identified urine protein-to-creatinine ratio (UPCR) <0.7 g/g as a clinically meaningful low proteinuria threshold that is associated with lower risk of kidney failure in patients with FSGS.”

DUPLEX (NCT03493685) was a phase 3, randomized trial of the efficacy and safety of sparsentan (800 mg/d; n = 184) vs maximum labeled dose irbesartan (300 mg/d; n = 187) in patients with FSGS that ran for 108 weeks. Investigators conducted post hoc analyses assessing the impact of sparsentan vs irbesartan on UPCR <0.7 g/g and observed kidney failure rates by proteinuria response. This analysis also included a real-world cohort of patients with FSGS from the RaDaR study (n = 386).

Radhakrishnan and colleagues found that patients in the sparsentan arm achieved UPCR <0.7 g/g earlier and more often vs those in the irbesartan arm (P <.0001). At week 108, 19.0% (n = 35) of patients receiving sparsentan (35/184) achieved UPCR <0.7 g/g compared with 11.2% of those receiving irbesartan (n = 21), corresponding to a relative risk (RR) of 1.7 (95% CI, 1.03–2.8). At any time through week 108, 37.5% (69/184) of patients receiving sparsentan achieved UPCR <0.7 g/g compared with 21.4% (n = 40) of patients receiving irbesartan, with an RR of 1.8 (95% CI, 1.3–2.4).1

“We are pleased to present new data from the pivotal DUPLEX Study, highlighting the correlation between proteinuria reduction and the potential of FILSPARI to reduce long-term kidney failure events,” Jula Inrig, MD, chief medical officer of Travere Therapeutics, said in a statement.2 “People living with FSGS face a serious and progressive disease that often leads to kidney failure and dialysis. The PARASOL Project has determined that reducing proteinuria to the lowest possible levels is key to protecting kidney function in FSGS, and these analyses from the DUPLEX Study reinforce its findings."

Investigators found that kidney failure occurred in 3.6% of patients (n = 4/112) who achieved a UPCR <0.7 g/g, compared with 11.2% of patients (n = 29/259) who did not achieve this threshold. The RR of kidney failure for those achieving UPCR <0.7 g/g was 0.52 (95% CI, 0.2–1.8). Furthermore, in the RaDaR cohort, patients who achieved UPCR <0.7 g/g at 24 months had lower risk of kidney failure over the next 60 months than those who did not reach this threshold (adjusted hazard rate [HR], 0.14; 95% CI, 0.05-0.38). Similarly, the 60 month-kidney failure risk for patients who reached UPCR <0.7 g/g at any time over 24 months was lower compared with those who did not reach this threshold (adjusted HR, 0.27; 95% CI, 0.16-0.45).1

"Together, these analyses indicate that the achievement of UPCR <0.7 g/g with sparsentan in DUPLEX is predictive of improved long-term kidney survival," Radhakrishnan and colleagues concluded.1

References

1. Radhakrishnan J, Gale DP, Gbadegesin RA, et al. Patients With Focal Segmental Glomerulosclerosis (FSGS) Reach Proteinuria <0.7 g/g More Often With Sparsentan vs Irbesartan in DUPLEX: Implications for Kidney Failure Risk. Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025. #TH-PO1219

2. Travere Therapeutics Announces Late-Breaking Data from Phase 3 DUPLEX Study of FILSPARI in FSGS Presented at the American Society of Nephrology (ASN) Kidney Week 2025. News release. November 6, 2025. https://ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-Announces-Late-Breaking-Data-from-Phase-3-DUPLEX-Study-of-FILSPARI-in-FSGS-Presented-at-the-American-Society-of-Nephrology-ASN-Kidney-Week-2025/default.aspx