Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis (DUPLEX)
In the largest FSGS trial to date, the dual endothelin-angiotensin blocker sparsentan lowered urine protein more than the standard blood-pressure drug irbesartan, but over two years it did not meaningfully slow the decline in kidney function compared with irbesartan.
Background
Focal segmental glomerulosclerosis (FSGS) frequently progresses to kidney failure, and there are no approved disease-specific therapies. Sparsentan is a single-molecule dual endothelin type A and angiotensin II type 1 receptor antagonist.
Study design
In this phase 3 trial, 371 patients aged 8-75 years with FSGS (without known secondary causes) were randomized to sparsentan (n=184) or the active control irbesartan (n=187) for 108 weeks. The interim surrogate endpoint was FSGS partial remission of proteinuria at 36 weeks; the primary endpoint was eGFR slope at final analysis.
Key findings
At 36 weeks, partial remission of proteinuria occurred in 42.0% of the sparsentan group versus 26.0% of the irbesartan group (P=0.009), a difference sustained through 108 weeks. However, there were no significant between-group differences in eGFR slope at 108 weeks (chronic slope difference 0.9 mL/min/1.73m2 per year, 95% CI -1.3 to 3.0).
Safety
Sparsentan and irbesartan had similar safety profiles, with a similar frequency of adverse events in the two groups.
Category
Research
Source
The New England Journal of Medicine
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