CSL Vifor announced topline primary efficacy results from the pivotal Phase 3 DUPLEX Study of sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), in focal segmental glomerulosclerosis (FSGS) from its partner Travere Therapeutics. At the end of the 108-week double-blind period, sparsentan was observed to have a 0.3 mL/min/1.73m2 per year (95% CI: -1.74, 2.41) favorable difference on eGFR total slope and a 0.9 mL/min/1.73m2 per year (95% CI: -1.27, 3.04) favorable difference on eGFR chronic slope compared to the active control irbesartan, which was not statistically significant. After 108 weeks of treatment, sparsentan achieved a mean reduction in proteinuria from baseline of 50%, compared to 32% for irbesartan.

Results from the two-year analysis demonstrated that sparsentan was well-tolerated and has shown a comparable safety profile to irbesartan. In the DUPLEX Study, a total of 371 patients were randomized 1:1 to receive either sparsentan or irbesartan, the active control. eGFR Primary Efficacy Endpoints: Chronic slope (primary endpoint in Europe): From week 6 to week 108 of treatment, following the initial acute effect of randomized treatment, the difference in eGFR chronic slope was 0.9 mL/min/1.73m2 per year in favor of sparsentan (-4.8 mL/min per 1.73 m2 per year; 95% CI: -6.34, -3.27) versus the active control irbesartan (-5.7 mL/min per 1.73 m2 per year; 95% CI:-7.20, -4.18), p=0.4203; Total slope (primary endpoint in US): From day one to week 108, the difference in eGFR total slope was 0.3 mL/min/1.73m2 per year in favor of sparsentan (-5.4 mL/min per 1.73 m2 per year; 95% CI: -6.89, -3.93) versus the active control irbesartan (-5.7 mL/min per 1.73 m2 per year; 95% CI: -7.20, -4.29), p=0.7491.

The secondary, topline exploratory and hard endpoints in the study trended favorably for sparsentan. Proteinuria Two-Year Exploratory Endpoints: Urine protein-to-creatinine ratio (UP/C): After 108 weeks of treatment, the change from baseline UP/C was 50% for sparsentan versus 32% for irbesartan. FSGS partial remission of proteinuria endpoint (FPRE): At week 108, 38% of patients on sparsentan achieved FPRE compared with 23% on irbesartan; Complete remission: 18% of patients on sparsentan versus 7% on irbesartan achieved complete remission of proteinuria (UP/C <0.3 g/g) at any time during the double-blind period.

A preliminary review of the safety results through 108 weeks of treatment indicate sparsentan has been generally well-tolerated and the overall safety profile in the study to date has been generally consistent between treatment groups. Travere Therapeutics intends to complete a full evaluation of the data from the DUPLEX Study and work with study investigators on future presentations and publication of the results at an upcoming medical meeting and/or in a peer-reviewed publication.