Concerns about the cardiovascular safety of conventional therapies for anemia in dialysis-dependent (DD)-CKD patients have prompted the development of alternatives. Roxadustat, an oral prolyl hydroxylase inhibitor of hypoxia-inducible factor, increases erythropoiesis by boosting endogenous erythropoietin and iron availability. Patients with DD-CKD with anemia were randomized 1:1 to oral roxadustat three times weekly or parenteral epoetin alfa per local clinic practice in an open-label phase 3 research. The first roxadustat dose was determined by the erythropoiesis-stimulating agent dose at screening for individuals who were already on it, and it was weight-based for those who were not. The key efficacy end goal was mean hemoglobin change from baseline averaged across weeks 2,852 for roxadustat versus epoetin alfa, regardless of rescue treatment usage, and noninferiority was assessed for (margin, 0.75 g/dl). Adverse occurrences (AEs) were investigated.
The mean age of the 2,133 patients randomized (n=1068 roxadustat, n=1065 epoetin alfa) was 54.0 years, with 89.1% on hemodialysis and 10.8%on peritoneal dialysis, respectively. The mean (95% CI) hemoglobin decrease from baseline with roxadustat was 0.77 (0.69 to 0.85) g/dl and 0.68 (0.60 to 0.76) g/dl with epoetin alfa, suggesting noninferiority (least-squares mean difference [95% CI], 0.09 [0.01 to 0.18]; P<0.001). The proportion of patients reporting 1 AE and 1 significant AE with roxadustat was 85.0% and 57.6%, respectively, and 84.5% and 57.5% with epoetin alfa. Roxadustat successfully improved hemoglobin in DD-CKD patients, with an AE profile equivalent to epoetin alfa.