RARE Daily

Travere Presents Late-Breaking, Phase 3 Data from Sparsentan in Two Rare Kidney Conditions

November 6, 2023

Rare Daily Staff

Travere Therapeutics reported additional data from two pivotal clinical studies demonstrating its drug Filspari has the potential to preserve kidney function and significantly delay time to kidney failure compared to an active comparator, suggesting long-term benefits in IgA nephropathy and focal segmental glomerulosclerosis.

Data from the phase 3 PROTECT and DUPLEX Studies were presented as late-breaking oral presentations at the American Society of Nephrology Kidney Week 2023 and simultaneously published in The Lancet and The New England Journal of Medicine.

“These data from PROTECT suggest that Filspari has the potential to significantly delay time to kidney failure, which based on recently published data is projected to be an additional eight years versus being treated with standard of care,” said Jula Inrig, chief medical officer of Travere Therapeutics.

IgA nephropathy (IgAN), also called Berger’s disease, is a rare progressive kidney disease 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), protein in the urine (proteinuria) and a progressive loss of kidney function. Other symptoms of IgAN may include swelling (edema) and high blood pressure. IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of kidney failure due to glomerular disease.

Filspari is a once-daily, oral medication designed to selectively target two critical pathways in the disease progression of IgAN. It is indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. The FDA granted accelerated approval for Filspari in IgAN in February.

Travere said that treatment with Filspari resulted in one of the slowest rates of kidney function decline in an IgAN trial of its kind. It said the data showed a beneficial effect on preserving kidney function was durable post washout. Treatment effects were consistent across baseline eGFR and proteinuria, supporting the potential for Filspari as a foundational treatment option across different stages of disease.

When imbalances between treatment arms were factored into pre-specified eGFR analyses (early treatment discontinuations and higher rates of rescue immunosuppression, both of which occurred more in the irbesartan arm) the beneficial effects of Filspari on kidney function preservation were strengthened.

Treatment with Filspari demonstrated lower rates of the composite endpoint of 40 percent decline in eGFR, kidney failure, or death compared to irbesartan.

Treatment with Filspari resulted in the largest magnitude of sustained reduction in proteinuria shown in a pivotal trial over two years with Filspari-treated patients achieving a mean reduction in proteinuria from baseline of 43 percent compared to 4 percent for irbesartan-treated patients.

More patients treated with Filspari achieved complete remission of proteinuria of less than 0.3 grams compared to those treated with irbesartan (31 percent vs 11 percent).

Filspari was well-tolerated with a safety profile that was consistent across all clinical trials conducted to date and comparable to the active control, irbesartan, including no drug-induced liver injury and no fluid overload.

Focal segmental glomerulosclerosis (FSGS) is a rare proteinuric kidney disorder in both children and adults that is estimated to affect more than 40,000 patients in the United States with similar prevalence in Europe. The disorder is defined by progressive scarring of the kidney and often leads to kidney failure. FSGS is 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, known as edema, as well as low blood albumin levels, abnormal lipid profiles and hypertension. There is currently no approved pharmacologic indicated for the treatment of FSGS.

Filspari is in phase 3 development in FSGS.

Travere said that treatment with Filspari demonstrated a clinically meaningful and durable reduction in proteinuria, with FSGS patients achieving a 50 percent reduction from baseline, compared to a 32 percent reduction with the active control irbesartan.

Filspari showed a consistent and sustained achievement of complete remission of proteinuria in 18.5 percent of patients on Filspari vs. 7.5 percent for irbesartan.

The combined hard endpoints of confirmed 50 percent reduction in eGFR, end-stage renal disease or death, trended in favor of Filspari with fewer patients progressing to kidney failure.

Filspari was well-tolerated with a safety profile that was consistent across all clinical trials conducted to date and comparable to the active control, irbesartan, including no drug-induced liver injury and no fluid overload.

“FSGS is an incredibly complex and heterogeneous rare kidney disease that can be difficult to study and currently has no approved pharmacologic treatment options,” said Michelle Rheault, director at the Division of Pediatric Nephrology, University of Minnesota Medical School and steering committee member for the DUPLEX clinical trial. “In the DUPLEX Study, which is the largest study in FSGS ever conducted, we are seeing for the first time a non-immunosuppressive medicine making a clinically meaningful impact in patients’ lives by reducing proteinuria, a proven indicator of kidney damage, by 50 percent.”

Stay Connected

Sign up for updates straight to your inbox.