Chugai Files for Japanese Approval of Sparsentan for IgA Nephropathy, Citing Significant Proteinuria Reduction
核心洞察
Chugai Pharmaceutical filed a new drug application in Japan for sparsentan, a dual endothelin and angiotensin II receptor antagonist, for the treatment of IgA nephropathy (搜索).
The global Phase III PROTECT study showed sparsentan reduced urine protein/creatinine ratio by 49.8% versus 15.1% for irbesartan at Week 36 (p<0.0001).
A Japanese Phase III study confirmed efficacy with a 58.5% reduction in UPCR, consistent with global findings and no new safety signals in Japanese patients.
Chugai Pharmaceutical Co., Ltd. announced on June 19, 2026, that it has filed a regulatory application with Japan's Ministry of Health, Labour and Welfare (MHLW) for sparsentan, an oral dual endothelin and angiotensin II receptor antagonist, for the treatment of patients with IgA nephropathy (搜索).
The submission marks a significant step toward addressing an unmet medical need in Japan, where approximately 33,000 patients live with IgA nephropathy (搜索), a designated intractable disease (No. 66) characterized by chronic glomerulonephritis driven by the deposition of glycosylation-aberrant IgA in the kidney glomeruli. Approximately 40% of patients progress to end-stage renal disease within 20 years of diagnosis, often requiring dialysis or kidney transplantation.
"In IgA nephropathy (搜索), a designated intractable disease, there are patients in whom proteinuria is not adequately controlled with existing treatments, and long-term decline in kidney function has remained an unmet challenge," said Dr. Osamu Okuda, President and CEO of Chugai. "Sparsentan has a novel mechanism of action that inhibits both the endothelin receptor and angiotensin II receptor, and has demonstrated a significant reduction in proteinuria in clinical studies, with results suggesting a potential benefit in preserving kidney function."
Dual Mechanism of Action
Sparsentan is an oral, small molecule that simultaneously inhibits endothelin receptor type A (搜索) (ETAR) and angiotensin II type 1 receptor (搜索) (AT1R). By targeting the endothelin pathway in addition to the renin–angiotensin (RA) system, sparsentan has been shown to provide a more potent reduction in proteinuria while maintaining once-daily dosing comparable to conventional RA system inhibitors.
Clinical Evidence Supporting the Filing
The regulatory application is supported by two pivotal studies: the global Phase III PROTECT study conducted across 18 countries, including South Korea and Taiwan, and the Japanese Phase III RE-021-001 study, both enrolling IgA nephropathy (搜索) patients with persistent proteinuria.
In the PROTECT study, sparsentan demonstrated a statistically significant improvement in the primary endpoint—the percent change from baseline in urine protein/creatinine ratio (UPCR) at Week 36—compared with the active control irbesartan (–49.8% vs –15.1%, p<0.0001). Results of the key secondary endpoint, the total slope of estimated glomerular filtration rate (eGFR) over time, suggested a potential long-term benefit in preserving kidney function.
Sparsentan was generally well tolerated, with a safety profile consistent with data from previous clinical studies. Treatment-emergent adverse events observed during the double-blind period in the sparsentan group included hypotension, hyperkalemia, dizziness, and peripheral edema.
In the Japanese Phase III RE-021-001 study, the primary endpoint—percent change from baseline in UPCR at Week 36—achieved a –58.5% reduction, consistent with findings from the global PROTECT study and demonstrating efficacy in Japanese patients. The safety profile was consistent with previously known findings, and no new safety signals specific to Japanese patients were identified.
Global Regulatory Status
Sparsentan received full FDA approval in the United States in September 2024 as FILSPARI for the treatment of IgA nephropathy (搜索), followed by standard marketing authorization in Europe in April 2025. In April 2026, FILSPARI also gained FDA approval to reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (搜索) (FSGS) without nephrotic syndrome, another rare kidney disease characterized by elevated proteinuria.
"Together with the convenience of once-daily dosing, we aim to support long-term disease management for patients and contribute to establishing a treatment foundation for IgA nephropathy (搜索)," Dr. Okuda added.