Roxadustat Efficacy and Safety in Patients Receiving Peritoneal Dialysis: Pooled Analysis of Four Phase 3 Studies

Abstract

Background/Objectives: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). Methods: This analysis pooled data from four phase 3, multicenter, randomized, open-label, active-comparator studies (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES). The primary endpoints evaluated were hemoglobin change from baseline (CFB) to Weeks 28–36 without rescue therapy and hemoglobin CFB to Weeks 28–52 regardless of rescue therapy use. Safety data were reported. Results: This analysis included 422 patients (215 roxadustat, 207 ESA). Hemoglobin CFB to Weeks 28–36 without rescue therapy and hemoglobin CFB to Weeks 28–52 regardless of rescue therapy achieved non-inferiority for roxadustat vs. ESAs. The mean weekly dose of roxadustat was maintained over time (Weeks 1–4, 3.86 mg/kg/week; Weeks 101–104, 3.27 mg/kg/week), whereas the mean weekly ESA dose increased by 24% (Weeks 1–4, 115.70 IU/kg/week; Weeks 101–104, 143.40 IU/kg/week). Fewer patients treated with roxadustat received intravenous iron supplementation and rescue therapy, and patients treated with an ESA required blood transfusions sooner. Roxadustat-treated patients experienced a greater decrease in low-density lipoprotein cholesterol levels relative to baseline vs. ESA-treated patients. Treatmentemergent adverse events were similar in both treatment groups. Major adverse cardiovascular event (MACE), MACE plus unstable angina or congestive heart failure, and all-cause mortality hazard ratios were <1; the lower limit of the 95% CIs was <0.6, and the upper limit was >1.3. Conclusions: Roxadustat was non-inferior to ESAs in correcting and maintaining hemoglobin levels, with stable dosing and a comparable safety profile, in anemic patients receiving PD.