Topline results from two-year primary efficacy endpoint in pivotal phase III DUPLEX Study of sparsentan in focal segmental glomerulosclerosis

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.

The Company will engage with regulators to explore a potential path forward for a supplemental New Drug Application (sNDA) in the U.S. Together with its collaborator CSL Vifor, the Company also plans to engage with the European Medicines Agency (EMA) to determine the potential for a subsequent variation to the Conditional Marketing Authorization (CMA) of sparsentan for the treatment of FSGS, subject to a review decision on the pending application for the CMA of sparsentan in IgA nephropathy.

For the last several years we have been leading development efforts in this area which has culminated in the largest interventional study conducted to-date in FSGS, and the only one comparing a candidate against an active control,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “We are disappointed that we did not achieve the primary efficacy endpoint in this study, but we did see results that trended favorably for sparsentan that we are further exploring to determine a potential path forward in FSGS. We are grateful for the patients, their caregivers, the investigators, clinical staff, the patient advocacy groups and our entire team at Travere who came together to support the DUPLEX Study.”

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: 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. 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.The secondary and topline exploratory endpoints, including renal outcomes, trended favorably for sparsentan in the study.

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.

The Company 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.