Japan approves Roxadustat for non-dialysis anemia in chronic kidney disease

Astellas Pharma and FibroGen have received approval from Japan‘s Ministry of Health, Labour and Welfare (MHLW) for the extended use of EVRENZO (roxadustat) in adults with anemia associated with chronic kidney disease (CKD) who are not on dialysis. This marks the second approval for roxadustat in Japan, following its initial approval in 2023 for adults with CKD-related anemia on dialysis. The expanded approval is a significant milestone for both companies, opening up new avenues for patients suffering from this debilitating condition.

Expanded Use of Roxadustat in Japan

Roxadustat’s newly approved indication extends its use beyond patients on dialysis, allowing it to be administered to a broader group of individuals with anemia due to CKD. This decision comes after the successful completion of three pivotal clinical studies involving more than 500 Japanese patients. These studies have demonstrated the efficacy of roxadustat in addressing anemia in non-dialysis patients, offering a promising alternative to existing treatments.

In his statement, Bernhardt G. Zeiher, Chief Medical Officer of Astellas Pharma, expressed enthusiasm about the approval. He highlighted that the new indication will enable even more patients to benefit from roxadustat, which has a unique oral administration and a novel mechanism of action. Zeiher stated, “We are delighted roxadustat is now approved in Japan for adults with anemia of CKD not on dialysis, as it allows even more patients to access this important new treatment option.”

Mechanism of Action: How Roxadustat Works

Roxadustat operates through an innovative mechanism of action, different from traditional erythropoiesis-stimulating agents (ESAs). It is an oral HIF-PH (hypoxia-inducible factor prolyl hydroxylase) inhibitor, designed to trigger the body’s natural response to low oxygen levels. This response stimulates the production of red blood cells and helps address the underlying causes of anemia, making roxadustat a crucial tool in CKD treatment.

Traditional treatments for anemia, such as ESAs, primarily rely on synthetic erythropoietin to stimulate red blood cell production. However, roxadustat works by mimicking the body’s natural hypoxic response to low oxygen levels, stimulating a cascade of biological processes that result in increased hemoglobin production. This offers a promising alternative for patients who may not respond well to other therapies.

Clinical Data and Study Results

The approval of roxadustat for non-dialysis patients is grounded in robust clinical trial data. A key study compared roxadustat to darbepoetin alfa, a widely used ESA, and successfully met its primary efficacy endpoint of non-inferiority. The study demonstrated that roxadustat could maintain hemoglobin levels over time in CKD patients not on dialysis, showing a potential benefit in improving patient outcomes.

Peony Yu, Chief Medical Officer of FibroGen, commented on the significance of this approval, noting that by making roxadustat available to both dialysis-dependent and non-dialysis patients, the companies are addressing a substantial unmet medical need in the CKD community. Yu further emphasized that the approval marks a continued effort to provide meaningful treatments for individuals living with anemia of CKD.

Dosing and Administration

Roxadustat is administered orally, which is a significant advantage over injectable therapies. The typical starting dose for adult patients is 50 mg, taken three times a week. After the initial dose, the treatment regimen may be adjusted based on the patient’s condition. The maximum dose for roxadustat should not exceed 3.0 mg/kg.

For patients transitioning from erythropoiesis-stimulating agents, the starting dose of roxadustat should be either 70 mg or 100 mg, administered three times per week, with dosage adjustments based on the patient’s response. This flexibility in dosing is designed to ensure optimal treatment for patients with varying degrees of anemia.

Future Prospects for Roxadustat in CKD Treatment

The extended approval of roxadustat is a significant step in expanding the treatment landscape for anemia associated with chronic kidney disease. The oral formulation and novel mechanism offer a new avenue for managing the condition, particularly in patients who are not on dialysis. This approval also reflects growing confidence in roxadustat as a treatment option in the broader CKD population.

As Astellas Pharma and FibroGen continue to work on expanding the reach of roxadustat, future studies and approvals could bring even greater benefits to patients with chronic kidney disease and anemia. The collaboration between the two companies aims to address a critical gap in treatment options and provide relief to millions affected by this complex and often under-treated condition.

With the recent approval of roxadustat in Japan for anemia of CKD not on dialysis, Astellas Pharma and FibroGen have made a significant stride in improving treatment options for a broad range of patients. By offering an oral alternative to traditional treatments and leveraging its unique mechanism of action, roxadustat could potentially transform the way anemia in CKD is managed, alleviating the burden on patients and healthcare systems alike. As more clinical data emerges, roxadustat may continue to play a pivotal role in the management of chronic kidney disease-related anemia globally.