Travere Misses Secondary Endpoint in Pivotal Trial Comparing Filspari to Generic in IgA Nephropathy
September 21, 2023
Rare Daily Staff
Travere Therapeutics reported topline two-year, confirmatory, secondary endpoint results from the company’s pivotal, head-to-head phase 3 PROTECT study of Filspari in IgA nephropathy versus irbesartan, narrowly missing statistical significance in a primary goal of the study.
Shares slumped 40 percent on the news in premarket trading. The FDA granted accelerated approval to Filspari in February 2023 for the treatment of IgA nephropathy. Travere will engage with regulators and expects to submit a supplemental New Drug Application in the first half of 2024 for full approval in the United States.
In the newly reported results, Filspari demonstrated long-term kidney function preservation and achieved a clinically meaningful difference in estimated glomerular filtration rate (eGFR) total and chronic slope versus irbesartan, but narrowly missed statistical significance in eGFR total slope while achieving statistical significance in eGFR chronic slope for purposes of regulatory review in the European Union.
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. IgAN is estimated to affect up to 150,000 people in the United States and is one of the most common glomerular diseases in Europe and Japan.
In the PROTECT study, a total of 404 patients with persistent proteinuria despite active angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) treatment, were randomized 1:1 to receive once daily oral doses of either Filspari or irbesartan, the active control. eGFR total and chronic slope are the secondary confirmatory endpoints for the United and the European Union, respectively. All topline efficacy endpoints favored Filspari as compared to irbesartan.
A preliminary review of the safety results through 110 weeks of treatment indicates Filspari was generally well-tolerated and the overall safety profile in the study has been consistent between treatment groups.
“The confirmatory results of the PROTECT study demonstrated treatment with Filspari resulted in the largest sustained reduction in proteinuria and one of the slowest rates of eGFR decline in a controlled study of IgAN patients, to date. This outcome is incredibly important for IgAN patients, who face the risk of progression to kidney failure in their lifetime,” said Eric Dube, president and CEO of Travere Therapeutics. “While eGFR total slope narrowly missed statistical significance, the overall evidence from PROTECT suggests potential long-term benefit of Filspari as a foundational treatment for patients with IgAN. Filspari has the potential to transform the treatment paradigm in this rare kidney disease, and we look forward to engaging with FDA to discuss our planned sNDA submission.”
Travere will complete a full evaluation of the data from the PROTECT Study and work with the study investigators on future presentations and publications of the results at an upcoming medical meeting and in a peer-reviewed publication.
In August 2022, the European Medicines Agency accepted for review the Conditional Marketing Authorization application of sparsentan for the treatment of IgAN. Together with its partner CSL Vifor, Travere anticipates a review opinion by the Committee for Medicinal Products for Human Use on the CMA application for sparsentan for the treatment of IgAN in the European Union around year-end.
Photo: Eric Dube, president and CEO of Travere Therapeutics
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