Benzinga | Aug 16, 2021 07:15AM EDT

Travere Therapeutics Announces Positive Topline Interim Results from the Ongoing Phase 3 PROTECT Study of Sparsentan in IgA Nephropathy

Travere Therapeutics, Inc. (NASDAQ:TVTX) today announced positive topline interim results from the ongoing pivotal Phase 3 PROTECT Study of sparsentan, an investigational product candidate for the treatment of IgA nephropathy (IgAN). The PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance, demonstrating a greater than threefold reduction of proteinuria from baseline after 36 weeks of treatment, compared to the active control irbesartan (p<0.0001). Preliminary results from the interim analysis suggest that to date in the study, sparsentan has been generally well-tolerated and consistent with the observed safety profile to date. Based on the results from the interim analysis, the Company plans to submit an application for accelerated approval in the U.S. in the first half of 2022 and also plans to submit an application for conditional marketing authorization in Europe.

"IgAN is a leading cause of end-stage kidney disease and there is a clear need for novel treatment options to slow the progression of this devastating rare kidney disorder," said Eric Dube, Ph.D., chief executive officer of Travere Therapeutics. "These data from the PROTECT Study further demonstrate sparsentan's ability to significantly reduce proteinuria and support its potential to become a new foundational treatment for people living with IgAN, if approved. We will continue our efforts to maintain high quality in this ongoing study, and we look forward to engaging with regulators as we prepare for accelerated approval submissions beginning in the first half of next year."

Consistent with prior guidance, the Company is providing limited data from the interim analysis to maintain trial integrity in the ongoing study. In the PROTECT Study, a total of 404 patients with persistent proteinuria despite active ACE or ARB treatment, were randomized 1:1 to receive once daily oral doses of either sparsentan or irbesartan, the active control. The study protocol provided for an unblinded interim analysis to evaluate the primary efficacy endpoint -- the change in proteinuria (urine protein-to-creatinine ratio) from baseline at Week 36 -- approximately 36 weeks following randomization of the first 280 patients. After 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8 percent, compared to a mean reduction in proteinuria from baseline of 15.1 percent for irbesartan-treated patients (p<0.0001).

"Sparsentan has now demonstrated in one of the largest interventional studies to date in IgAN, a statistically robust and clinically meaningful proteinuria reduction relative to a current standard of care," said Noah Rosenberg, M.D., chief medical officer of Travere Therapeutics. "These data build upon our Phase 2 DUET and Phase 3 DUPLEX studies in FSGS and further strengthen the support for our novel approach with sparsentan as a dual endothelin-angiotensin receptor antagonist being developed for rare kidney disorders. I want to thank all the patients, their families, as well as the investigators and site staff who continue to participate in this ongoing landmark study in IgAN."

Secondary efficacy endpoints include the rate of change in estimated glomerular filtration rate (eGFR) following the initiation of randomized treatment over 58-week and 110-week periods, as well as the rate of change in eGFR over 52-week and 104-week periods following the first six weeks of randomized treatment. The Company believes that preliminary eGFR data available at the time of the interim analysis are indicative of a potential clinically meaningful treatment effect after two years of treatment. Per study protocol, patients will continue in a blinded manner in the PROTECT Study to fully assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis. Topline results from the confirmatory endpoint analysis are expected in the second half of 2023.

A preliminary review of the interim safety results indicates that to date in the study, both treatment groups were generally well tolerated, and sparsentan appeared consistent with the previously observed safety profile with no new safety signals emerging.

The Company also remains on track to provide a regulatory update on its pivotal Phase 3 DUPLEX Study of sparsentan for the treatment of focal segmental glomerulosclerosis (FSGS) during the third quarter of 2021.