Travere Therapeutics Submits NDA for Sparsentan for the Treatment of IgA Nephropathy

Travere Therapeutics, Inc. recently announced it has submitted a New Drug Application (NDA) to the US FDA under Subpart H for accelerated approval of sparsentan for the treatment of IgA nephropathy (IgAN).

“There is a clear need for novel treatment options that can reduce proteinuria and slow the devastating progression toward end-stage kidney disease for people living with IgA nephropathy,” said Eric Dube, PhD, President and Chief Executive Officer of Travere Therapeutics. “The submission of this NDA marks an important milestone on our path to potentially making sparsentan, if approved, a new treatment standard for the rare kidney disease community, and we look forward to working with the FDA during the upcoming review process.”

The NDA submission is supported by positive interim results from the ongoing pivotal Phase 3 PROTECT Study, a global, randomized, active-controlled study evaluating the safety and efficacy of sparsentan in a total of 404 patients with IgAN, as well as data from additional clinical trials and pre-clinical testing of sparsentan. The Company expects to receive notice regarding the acceptance of the NDA, as well as the timeline for NDA review, from the FDA in May 2022.

IgA nephropathy (IgAN), also called Berger’s disease, is a rare kidney disorder characterized by the buildup of immunoglobulin A (IgA), a protein that helps the body fight infections, in the kidneys. The deposits of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to blood in the urine (hematuria), and protein in the urine (proteinuria). Other symptoms of IgAN may include kidney pain, swelling (edema) and high blood pressure.

IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of end-stage kidney disease (ESKD). IgAN is estimated to affect more than 100,000 people in the U.S. and is one of the leading causes of acute nephritis in Europe and Japan. There are currently no approved non-immunosuppressive treatments indicated for IgAN.

The ongoing PROTECT Study is one of the largest interventional studies to date in IgAN. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of 400mg of sparsentan, compared to 300mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite available ACE or ARB therapy. In August 2021, the Company announced the PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance. 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). 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. Preliminary results at the time of the interim assessment suggested that sparsentan had been generally well-tolerated to date in the study and consistent with its overall observed safety profile. The PROTECT Study is fully enrolled and is scheduled to continue as planned on a blinded basis to 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.

Sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), is a novel investigational product candidate selectively targeting the endothelin A receptor (ET_AR) and the angiotensin II subtype 1 receptor (AT₁R). Pre-clinical data have shown that blockade of both endothelin type A and angiotensin II type 1 pathways in forms of rare chronic kidney disease, reduces proteinuria, protects podocytes and prevents glomerulosclerosis and mesangial cell proliferation. Sparsentan has been granted Orphan Drug Designation for the treatment of IgAN and FSGS in the US and Europe.

Sparsentan is currently being evaluated in the pivotal Phase 3 DUPLEX Study for the treatment of focal segmental glomerulosclerosis (FSGS) and the pivotal Phase 3 PROTECT Study for the treatment of IgAN. In February 2021, the Company announced that the ongoing pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its pre-specified interim FSGS partial remission of proteinuria endpoint (FPRE) with statistical significance. FPRE is a clinically meaningful endpoint defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 g/g and a >40 percent reduction in UP/C from baseline. After 36 weeks of treatment, 42.0 percent of patients receiving sparsentan achieved FPRE, compared to 26.0 percent of irbesartan-treated patients (p=0.0094). Preliminary results from the interim analysis suggest that at the time of the interim assessment, sparsentan had been generally well-tolerated and shown a comparable safety profile to irbesartan. In the Phase 2 DUET Study of sparsentan in FSGS, the combined treatment group met its primary efficacy endpoint, demonstrating a greater than two-fold reduction in proteinuria compared to irbesartan, and was generally well tolerated after the eight-week, double-blind treatment period. Irbesartan is part of a class of drugs used to manage FSGS and IgAN in the absence of an approved pharmacologic treatment. If approved for both indications, sparsentan could potentially be the first medicine approved for both FSGS and IgAN.

At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com.