Ligand Pharmaceuticals has announced that its partner Travere Therapeutics has received accelerated approval from the US Food and Drug Administration (FDA) for FILSPARI (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression.
This is generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.
This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether FILSPARI slows kidney function decline.
FILSPARI, a once-daily oral medication, is designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II) and is the first and only non-immunosuppressive therapy approved for the treatment of this condition. IgAN is a rare kidney disease and a leading cause of kidney failure due to glomerular disease, affecting up to 150,000 people in the US, with approximately 30,000 to 50,000 of such patients estimated to be addressable under the indication approved via accelerated approval.
"We are delighted to see the approval of sparsentan, now FILSPARI, which represents a significant step forward in improving the lives of patients living with IgA nephropathy,” said Todd Davis, CEO of Ligand Pharmaceuticals. “Our partnership with Travere has been a remarkable journey, and we are proud to have played a part in bringing this innovative treatment to market. Congratulations to the entire team at Travere on this accomplishment."
Under Ligand’s license agreement with Travere for sparsentan, Ligand is entitled to receive a net $15.3 million milestone on this FDA approval, other potential milestone payments and net royalties of 9% on future global net product sales of sparsentan.
“The accelerated approval of FILSPARI is a significant milestone on our path to advancing a transformative treatment for the IgA nephropathy community,” said Eric Dube, PhD, President and CEO of Travere Therapeutics. “As a first-of-its-kind, non-immunosuppressive therapy, we believe FILSPARI has the potential to ultimately become the new standard of care for IgA nephropathy and offer hope to those living with this condition who until now have had few treatment options.”
The approval of FILSPARI, granted under the FDA’s accelerated approval pathway, is based on clinically meaningful and statistically significant improvements in proteinuria compared to an active comparator in the pivotal and ongoing Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN.
As a first-of-its-kind, non-immunosuppressive therapy, we believe FILSPARI has the potential to ultimately become the new standard of care for IgA nephropathy
The PROTECT Study is a global, randomised, multicentre, double-blind, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of FILSPARI, compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite maximal tolerated ACE or ARB therapy.
In August 2021, Travere announced positive topline interim results that were based on the pre-specified, primary analyses set which showed that after 36 weeks of treatment, patients receiving FILSPARI achieved a mean reduction in proteinuria from baseline of 49.8%, compared to a mean reduction in proteinuria from baseline of 15.1% for irbesartan-treated patients (p<0.0001).
Per request from the FDA, the efficacy data contained in the FDA-approved label is a post-hoc sensitivity analysis that evaluates the first 281 randomised patients, a subset of the full trial population.
The mean reduction in proteinuria from baseline in the post-hoc sensitivity analysis is 45% for FILSPARI versus 15% for the active control, irbesartan. Both the pre-specified and post-hoc sensitivity analyses have demonstrated that FILSPARI achieves a rapid and sustained reduction in proteinuria, with statistically significant and clinically meaningful improvement compared to the active comparator irbesartan.
Per the study protocol, patients continue in a blinded manner in the PROTECT Study to fully assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis.
Results from the confirmatory endpoint analysis are expected in the fourth quarter of 2023.
