FDA Grants Accelerated Approval to Sparsentan for Progressive Form of Kidney Disease

The FDA granted accelerated approval to sparsentan (Filspari; Travere Therapeutics, Inc., and Ligand Pharmaceuticals) the first and only non-immunosuppressive therapy approved to treat IgA nephropathy (IgAN), according to a press release.

Oral sparsentan targets the endothelin-1 and angiotensin 2 pathways—both of which promote disease progression of IgAN—and is indicated to decrease proteinuria (protein in the urine) in patients at risk for disease progression. This is generally defined as having a urine protein-to-creatinine ratio (UPCR) that is 1.5 g/g or less.

"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, in the press release. Ligand is partnering with Traverse on sparsentan, and they have a license agreement to receive $15.3 million for the FDA approval.

Investigators are currently conducting the PROTECT Study, an ongoing phase 3, global, randomized, multicenter, double-blind, active-controlled clinical trial to measure safety outcomes and sparsentan’s efficacy in slowing kidney decline. Investigators are comparing 400 mg of sparsentan compared to 300 mg of irbesartan for patients with IgAN and proteinuria, despite maximum tolerated angiotensin-converting enzyme (ACE) or angiotensin receptor blocker (ARB) therapy.

In August 2021, after 36 weeks of treatment, Traverse reported that proteinuria was reduced by 49.8% from baseline with sparsentan. The mean reduction in proteinuria with irbesartan-based treatment was only 15.1%.

These preclinical results suggest that sparsentan met its pre-specified primary efficacy endpoint, demonstrating clinically meaningful and statistically significant improvements in proteinuria. Topline results for the 2-year confirmation endpoints are expected at the end of 2023, which support traditional FDA approval of sparsentan, according to investigators at Travere.

“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,” said Eric Dube, PhD, president and CEO of Travere Therapeutics, in the press release.

The most common adverse events (AEs) occurring in 5% or more of patients were peripheral edema, hypotension and orthostatic hypotension, dizziness, hyperkalemia, and anemia. The medication may also increase the risk of liver injury and birth defects; therefore, it is available via a Risk Evaluation and Mitigation Strategy (REMS) approved by the FDA.

Nearly 150,000 people in the United States suffer from IgAN (Berger disease), a rare and progressive kidney disease that can cause kidney failure because of glomerular disease. IgAN occurs when protein immunoglobulin A (IgA) builds up in the kidneys, which worsens kidney filtration functions and leads to hematuria, proteinuria, and eventual kidney failure.

“The accelerated approval of Filspari is a significant milestone on our path to advancing a transformative treatment for the IgA nephropathy community,” Dube said in the press release.

Reference

Ligand Pharmaceuticals Incorporated. Ligand’s Partner Travere Therapeutics Announces FDA Accelerated Approval of FILSPARI™ (sparsentan), the First and Only Non-immunosuppressive Therapy for the Reduction of Proteinuria in IgA Nephropathy. Febraury 17, 2023. Accessed on February 21, 2023. https://www.businesswire.com/news/home/20230217005377/en