Travere Therapeutics announced that its confirmatory Phase 3 trial evaluating Filspari (sparsentan) for IgA nephropathy (IgAN) narrowly missed its primary endpoint. The study, involving 404 patients, compared Filspari to irbesartan, a commonly used blood pressure medication in managing IgAN. While the data indicated a slower decline in kidney function among patients receiving Filspari over 24 months, the results fell just short of statistical significance (p=0.058).
Trial Design and Results
The Phase 3 trial randomized patients with IgAN to either Filspari, a daily oral medication, or irbesartan. The primary endpoint assessed the change in estimated glomerular filtration rate (eGFR) over 24 months. Secondary endpoints included proteinuria reduction and safety assessments. Initial data, which led to accelerated approval in February, demonstrated a 50% reduction in proteinuria, a key biomarker of kidney function, after nine months of treatment. However, the 24-month data on eGFR, a more direct measure of kidney function, did not achieve the pre-specified level of statistical significance.
Clinical Context and Implications
IgA nephropathy is a rare kidney disease characterized by the buildup of immunoglobulin A (IgA) in the kidneys, leading to inflammation and potential kidney damage. Current treatment strategies often involve managing blood pressure and reducing proteinuria. The accelerated approval of Filspari was based on its ability to reduce proteinuria, a surrogate marker for kidney function. The full approval was contingent upon demonstrating a statistically significant benefit on kidney function decline in the confirmatory trial. The company will now need to discuss the implications of these results with regulatory authorities.
