Background Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for treatment of anaemia of chronic kidney disease (CKD). Methods This randomised, open-label, active-controlled phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non–dialysis-dependent (NDD) CKD patients with anaemia for ≤104 weeks. Doses were titrated to correct and maintain haemoglobin within 10.0–12.0 g/dL. The primary endpoint was haemoglobin response in the full analysis set (FAS), defined as haemoglobin ≥11.0 g/dL and haemoglobin change from baseline (CFB) ≥1.0 g/dL in patients with baseline haemoglobin >8.0 g/dL or CFB ≥2.0 g/dL in patients with baseline haemoglobin ≤8.0 g/dL during the first 24 weeks of treatment without rescue therapy (noninferiority margin, -15%). Key secondary endpoints included change in low-density lipoprotein (LDL), time to first intravenous iron use, change in mean arterial pressure (MAP), and time to hypertension occurrence. Adverse events were assessed. Results Of 616 randomised patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Haemoglobin response with roxadustat was noninferior to DA (roxadustat: 256/286, 89.5% vs. DA: 213/273, 78.0%, difference 11.51%, 95% confidence interval, 5.66-17.36%). Roxadustat maintained haemoglobin for up to 2 years. Roxadustat was noninferior to DA for change in MAP and time to occurrence of hypertension and superior for change in LDL and time to first intravenous iron use. Safety profiles were comparable between groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACE) and MACE + (MACE: 0.81 [0.52, 1.25], P = 0.339; MACE+: 0.90 [0.61, 1.32], P = 0.583). Conclusion Roxadustat is a viable option to treat anaemia in NDD CKD patients maintaining haemoglobin levels for up to 104 weeks.

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Introduction: Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with endstage kidney disease on dialysis for at least 4 months. Methods: Patients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0-12.0 g/dL during the treatment period (day 1 up to 52--104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28-36 without rescue therapy and hemoglobin CFB to the average of weeks 28-52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively. Results: Of 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat -ESA) for hemoglobin CFB to weeks 28-36 (without rescue therapy) and CFB to weeks 28-52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating noninferiority of roxadustat to ESA (non-inferiority margin of -0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28-36 were 84.2% (roxadustat) and 82.4% (ESA).

Anaemia is an important component of diabetic nephropathy but only recently has it attracted the attention of diabetologists and nephrologists. In diabetic patients, anaemia is the result of diminished erythropoietin production and, to a lesser degree, of increased excretion of erythropoietin in the urine, whereas erythropoietin responsiveness remains unchanged. Although erythropoietin concentrations are predictive of the rate of progression of renal disease, epidemiological studies have failed to show lower haemoglobin concentrations in patients with diabetic compared with non-diabetic renal disease with impaired renal function. However, inappropriately low erythropoietin concentrations and anaemia have been reported in subcohorts of diabetic patients. Further studies are required to determine whether reversal of anaemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, retinopathy and peripheral arterial disease.

Introduction: This integrated phase 3 analysis examined efficacy and cardiovascular safety for roxadustat vs erythropoiesis-stimulating agents (ESAs) in dialysis-dependent patients.Methods: Efficacy and safety results from four phase 3, randomized, open-label studies comparing roxadustat to ESAs (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES) in dialysis-dependent patients with anemia of chronic kidney disease (CKD) were evaluated by study, pooled population and in two subgroups: incident dialysis and stable dialysis. The primary efficacy endpoint per study was hemoglobin change from baseline (CFB) to weeks 28-36 using leastsquares mean difference (LSMD) without rescue therapy. Pooled safety endpoints included time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality [ACM]) and MACE? (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE? were evaluated for non-inferiority at 1.8 and 1.3 margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized. Results: In total, 4714 patients were randomized (2354 roxadustat; 2360 ESA). Hemoglobin CFB to weeks 28-36 achieved non-inferiority for roxadustat vs ESA in each study. Roxadustat was non-inferior to ESA for risks for MACE and MACE? in the entire cohort (MACE: HR 1.09, 95% CI 0.95-1.26; MACE? : HR 0.98, 95% CI 0.86-1.11) and similar to the incident dialysis and stable dialysis subgroups; ACM results were consistent with MACE and MACE? (HR 1.13,