Travere Achieves Interim Proteinuria Endpoint in Ongoing Study of Sparsentan in FSGS

Rare Daily Staff

Travere Therapeutics reported that its ongoing pivotal phase 3 DUPLEX study of sparsentan in focal segmental glomerulosclerosis achieved its pre-specified interim partial remission of proteinuria endpoint after 36 weeks of treatment.

Focal segmental glomerulosclerosis (FSGS) is a rare kidney disorder characterized by proteinuria, where protein leaks into the urine due to a breakdown of the normal filtration mechanism in the kidney. Once in the urine, protein is considered to be toxic to other parts of the kidney, especially the tubules, and is believed to contribute to further disease progression. Other common symptoms include swelling in parts of the body, as well as low blood albumin levels, abnormal lipid profiles and hypertension. The disorder is defined by progressive scarring of the kidney and often leads to end-stage kidney disease (ESKD). It is estimated to affect up to 40,000 patients in the U.S. with similar prevalence in Europe.

Reduction in proteinuria appears to be beneficial in the treatment of FSGS and may be associated with a decreased risk of progression to ESKD. Achieving FSGS partial remission of proteinuria endpoint (FPRE) appears to be associated with long-term preservation of renal function in patients with FSGS.

FSGS is currently managed with angiotensin receptor blockers, angiotensin converting enzyme inhibitors, steroids or calcineurin inhibitors. Travere’s experimental candidate sparsentan functions as a high affinity dual-acting antagonist of both the endothelin type A and angiotensin II type 1 receptors, in a single molecule. Preclinical data have shown that blockade of both pathways in forms of rare chronic kidney disease, reduces proteinuria, protects podocytes and prevents glomerulosclerosis and mesangial cell proliferation.

The ongoing DUPLEX study is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled phase 3 clinical trial assessing the efficacy and safety of sparsentan in 371 patients ages 8 to 75 years with primary FSGS. After a two-week washout period, patients are randomized 1:1 to receive either sparsentan or irbesartan, the active control. The study protocol provides for an unblinded analysis of at least 190 patients to be performed after 36 weeks of treatment to evaluate the interim efficacy endpoint—the proportion of patients achieving a FSGS partial remission of proteinuria endpoint (FPRE) The confirmatory endpoint of the study is the change in slope of estimated glomerular filtration rate (eGFR) from baseline after 108 weeks of treatment.

The interim results showed that patients receiving sparsentan achieved a statistically significant response on the interim proteinuria endpoint compared to irbesartan after 36-weeks of treatment. Preliminary results from the interim analysis also suggest that to date, sparsentan has been generally well-tolerated and has shown a comparable safety profile to irbesartan. Based on the data from the interim analysis, Travere intends to pursue submissions for accelerated approval of sparsentan for FSGS. The company also plans to continue its engagement with regulators in the first half of 2021 to discuss the ongoing study and to establish next steps for filing with the available data set.

“For decades people living with FSGS have faced daily challenges in controlling proteinuria and a fear of progressing to transplant or dialysis because current treatment options are not enough,” said Eric Dube, CEO of Travere Therapeutics. He said the interim results demonstrate treatment with sparsentan can lead to significantly greater reductions in proteinuria compared to current standard of care.

Travere is also evaluating sparsentan for the treatment of IgA nephropathy in the ongoing pivotal phase 3 PROTECT study, and topline efficacy data from the 36-week interim proteinuria endpoint analysis from that study are anticipated in the third quarter of 2021.

Sparsentan has been granted Orphan Drug designation for the treatment of FSGS in the U.S. and Europe. Sparsentan has also been granted Orphan Drug designation for the treatment of IgAN in the U.S. and has received a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products on the company’s application for Orphan Drug designation for IgAN in Europe.

Photo: Eric Dube, CEO of Travere Therapeutics