Michelle Rheault, MD, Pediatric Nephrologist at the University of Minnesota, discusses data from the DUPLEX study testing sparsentan to treat patients with focal segmental glomerulosclerosis (FSGS).
FSGS is a rare kidney disorder characterized by progressive scarring of the glomeruli. FSGS may cause non-specific signs and symptoms, including proteinuria, elevated levels of creatinine, and swelling. The condition often leads to kidney failure. In many cases the cause of FSGS can not be determined. Some cases may be associated with congenital kidney defects, urine backing up into the kidneys, obesity, obstructive sleep apnea, sickle cell anemia, or viruses.
At the American Society of Nephrology 2025 Kidney Week, new data was announced from the DUPLEX (NCT03493685) clinical trial. This study is a phase 3, randomized, multicenter, double-blind, parallel, active-control trial comparing sparsentan to an angiotensin receptor blocker (irbesartan) in patients with FSGS. Sparsentan is a dual endothelin and angiotensin II receptor antagonist that reduces kidney inflammation and proteinuria.
A previous study determined that urine protein-to-creatinine ratio (UPCR) below 0.7 g/g was a clinically meaningful proteinuria target in FSGS. The new data showed that 37.5% of sparsentan-treated patients achieved proteinuria below 0.7 g/g compared with 21.4% of those treated with irbesartan. Regardless of treatment type, patients who achieved UPCR below 0.7 g/g were less likely to reach kidney failure.
In a U.K. based cohort of the study [(U.K. National Registry of Rare Kidney Disease (RaDaR)] achieving UPCR below 0.7 g/g at 24-months was associated with lower risk of kidney failure over an additional 60-months of follow up. Similar results were observed for those who achieved UPCR below 0.7 g/g at any time over 24-months.
Long term use of sparsentan also showed promise. After five years of treatment, the DUPLEX Study demonstrated that treatment with sparsentan resulted in a clinically meaningful and durable reduction in proteinuria, with FSGS patients achieving a 50% reduction from baseline UPCR, compared to a 32% reduction with the maximum labeled dose of irbesartan. This translates to a 26% relative reduction in UPCR for sparsentan-treated patients compared to the maximum labeled dose of irbesartan at 24 months.
Within the RaDaR cohort, robust reductions in the risk of kidney failure were observed for patients achieving complete remission (UPCR below 0.3 g/g) and proteinuria below 0.7 g/g at 24 months. All reductions in UPCR correlated to a reduction in risk of kidney failure events at 5 years. When applied to the DUPLEX Study, the 26% relative reduction in UPCR for patients treated with sparsentan compared to irbesartan, correlates to a significant and clinically meaningful reduction in 5-year risk of kidney failure of 24%.
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To learn more about FSGS and other rare kidney conditions, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/
