Clinical Trial: Sparsentan for Treatment of IgA Nephropathy

Jula Inrig, MD, Chief Medical Officer at Travere Therapeutics, discusses a clinical trial that tested sparsentan for treatment of IgA nephropathy, compared to traditional RAS inhibitors. IgA nephropathy (IgAN) is a rare kidney disorder that occurs when immunoglobulin A (IgA), a protein that helps the body fight infections, settles in the kidneys. In the early stages, IgA nephropathy has no symptoms. The first sign of this condition may be blood in the urine. End-stage kidney disease may develop. In most instances, the cause of this condition is unknown; however, certain disorders have been linked with IgA nephropathy, such as cirrhosis of the liver, celiac disease, and HIV infection. Familial IgA nephropathy is linked to genetic material on the long arm of chromosome 6 (6q22-23). Current management of the disease involves medications that block abnormal hormones in the kidney, or renin-angiotensin system (RAS) inhibitors. In severe cases, steroids or immunosuppressants may also be used. Therapies that address the underlying cause of IgA nephropathy and the protein deposition in the kidneys are currently being developed. Sparsentan is a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), two hormones that cause kidney damage in this disease. As Dr. Inrig explains, blocking them can preserve kidney structure and function, as well as reduce proteinuria. Phase 3 PROTECT study was a global, randomized, multicenter, double-blind, parallel-arm, active controlled clinical trial. Its goal was to evaluate the safety and efficacy of sparsentan (400mg) compared to RAS inhibitor irbesartan (300mg) in adult patients IgAN. Sparsentan demonstrated significant reduction in proteinuria, with a mean reduction of 49.8 percent, compared to a mean reduction of 15.1 percent in the RAS inhibitor group. Sparsentan was also observed to better improve kidney function over time when compared to the alternative treatment. Sparsentan was granted Accelerated Approval by the U.S. Food and Drug Administration based on these results. The trial continued on for 2 years, showing a positive treatment effect on preserving kidney function. After 1 year, patients had 1.7 mL greater kidney function, and 3.7 mL greater at the 2 year mark. The company is currently looking into a submission to the FDA for full approval. Chapters: IgA Nephropathy Overview 00:00 Cause of Disease 2:30 Current Management 3:33 Sparsentan Overview 4:51 Next Steps 6:31