Oral roxadustat three times weekly in ESA-naïve and ESA-converted patients with anemia of chronic kidney disease on hemodialysis: Results from two phase 3 studies

Abstract

Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor approved in China for anemia of dialysis-dependent chronic kidney disease (CKD). Japanese hemodialysis patients with anemia of CKD previously naïve to, or converted from, erythropoiesis-stimulating agents (ESAs) were enrolled in two open-label, noncomparative studies of titrated oral roxadustat administered three times weekly. ESA-naïve patients (n = 75) were randomized to roxadustat (initial dose, 50 or 70 mg) for 24 weeks; ESA-converted patients (n = 164) were assigned to roxadustat (initial dose, 70 or 100 mg based on prior ESA dose) for 52 weeks. Efficacy outcomes included average hemoglobin (Hb, weeks 18-24 or 46-52), change of Hb from baseline to weeks 18 to 24 (ΔHb18-24) or weeks 46 to 52 (ΔHb46-52), and maintenance rate (proportion of patients who achieved average Hb of 10.0-12.0 g/dL for weeks 18-24 or weeks 46-52). Treatment-emergent adverse events (TEAEs) were monitored. Mean (SD) Hb was 10.93 (0.79) g/dL (weeks 18-24) (ESA-Naïve Study), and 10.93 (0.69; weeks 18-24) g/dL and 11.11 (0.67; weeks 46-52) g/dL (ESA-Converted Study). Mean (SD) ΔHb18-24 was 2.26 (1.02) g/dL (ESA-Naïve Study) and −0.03 (0.90) g/dL (ESA-Converted Study); mean (SD) ΔHb46-52 was 0.12 (0.83) g/dL (ESA-Converted Study). The overall maintenance rate was 73.0% (54/74) (ESA-Naïve Study) (weeks 18-24), and 79.1% (129/163; weeks 18-24) and 71.2% (116/163; weeks 46-52) (ESA-Converted Study). Nasopharyngitis was the most common TEAE. Two deaths, considered unrelated to roxadustat, occurred in the ESA-Converted Study. Roxadustat effectively corrected and maintained Hb, regardless of previous ESA treatment, in Japanese anemic CKD patients on hemodialysis.