Recently, Novartis announced that its innovative product Atrasentan Hydrochloride Tablets (Proprietary Name: VANRAFIA) has been approved by the National Medical Products Administration (NMPA) for reducing proteinuria in adult patients with primary immunoglobulin A nephropathy (IgA nephropathy) who are at risk of rapid disease progression. This marks the first non-immunologic therapy for IgA nephropathy in China, and the only highly selective endothelin-A (ETA) receptor antagonist approved domestically, representing a milestone that may reshape the long-term management of the disease.

IgA nephropathy is the most common primary glomerulonephritis worldwide, with an estimated 4 million patients in China alone. The disease predominantly affects young adults aged 20 to 30, who are often at a critical stage of social and family responsibilities. Its early course is typically insidious, presenting mainly with hematuria or proteinuria. Diagnosis often requires renal biopsy, but due to patient concerns, biopsy rates remain low in China, leading to delayed diagnosis and missed opportunities for early intervention. Studies show that about half of patients with persistent proteinuria progress to end-stage renal disease within 10 to 20 years of diagnosis, requiring lifelong dialysis or kidney transplantation.

Current treatment options rely on RAS inhibitors, corticosteroids, and immunosuppressants. However, these approaches have limitations in achieving long-term proteinuria control and delaying kidney function decline, with side effects that cannot be overlooked. As such, there is an urgent unmet need for safer and more effective baseline therapies.

The approval of atrasentan is grounded in a deeper understanding of IgA nephropathy’s pathophysiology. Research has identified overactivation of the endothelin system, particularly the ETA receptor, as a key driver of disease progression, leading to increased intraglomerular pressure, inflammatory infiltration, fibrosis, and podocyte loss. By selectively blocking the ETA receptor, atrasentan effectively reduces proteinuria, mitigates inflammation, and slows fibrosis, thereby providing multifaceted renal protection. Its high selectivity also avoids the sodium and fluid retention associated with non-selective endothelin receptor antagonists.

The global Phase III ALIGN trial further confirmed its clinical value. Results showed that patients experienced reductions in proteinuria as early as week 6 of treatment, and by week 36, the atrasentan group achieved a 36.1% reduction in 24-hour urine protein-to-creatinine ratio (UPCR) compared with placebo (P<0.0001). Atrasentan demonstrated good safety and tolerability. Given that proteinuria is a key surrogate marker of disease progression, its significant reduction suggests atrasentan may delay the onset of kidney failure.

Experts believe the introduction of this breakthrough therapy fills an important gap in non-immunologic treatment options for IgA nephropathy in China, offering clinicians a new choice. As a non-steroidal baseline drug, atrasentan can be used alone or in combination with existing regimens to provide more robust long-term disease control. Notably, atrasentan was also granted accelerated approval by the U.S. FDA in April 2025 for the same indication.

The compound patent for atrasentan (CN1091768C) expired on February 12, 2017, and no other patents related to atrasentan were found on China’s Listed Drugs Patent Information Registration Platform. In the U.S. Orange Book, however, four groups of related patents are recorded:

(1) US8623819B2, titled “Therapy for complications of diabetes”, which relates to the use of atrasentan for treating diabetic complications. No corresponding Chinese patent family exists.

(2) US10016393B2 and US9364458B2, titled “Stabilized pharmaceutical dosage forms comprising atrasentan”, which concern formulations of atrasentan. A corresponding Chinese family member exists (CN105517541A), but it has been deemed withdrawn.

(3) US11874283B2, titled “Method and compositions for the treatment and detection of endothelin-1 related kidney diseases”, which relates to the use of atrasentan in treating HIV-associated nephropathy (HIVAN) and/or focal segmental glomerulosclerosis (FSGS). This patent has not entered China.

(4) US12370174B2, US11491137B2, US11998526B2, and US12121509B2, titled “Methods of improving renal function”, which relate to the use of atrasentan for treating IgA nephropathy. Three corresponding Chinese family members (CN113272013A, CN116173014A, and CN116327758A) are currently under substantive examination. Due to restrictions under Chinese patent law regarding protectable subject matter, if granted, they are expected to take the form of use claims for the preparation of a medicament for treating IgA nephropathy.

Since the compound patent for atrasentan has expired, the formulation patents have not been granted in China, and the IgA-use patents—even if granted—would face inherent weaknesses in infringement determination, they would provide only limited protection for the product. Therefore, it is anticipated that multiple domestic generic companies will enter the market for atrasentan production and sales, which would undoubtedly be a great benefit for the many patients suffering from IgA nephropathy.