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.

Roxadustat for CKD-related Anemia in Non-dialysis Patients

“…HIF stabilizers have been approved for the treatment of CKD-related anemia in China and Japan, including roxadustat, which has been approved in China to treat anemia in patients with DD-CKD and NDD-CKD 16,17 and in Japan for patients with DD-CKD. 18 We evaluated the efficacy and safety of roxadustat vs. placebo for the treatment of CKD-related anemia in patients with NDD-CKD.…”

Effect of Kidney Function and Dialysis on the Pharmacokinetics and Pharmacodynamics of Roxadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor

“…For all patients, a meal was provided approximately 3 h before administration of roxadustat, after which food and water were not allowed before dosing. After dosing, patients had to refrain from food and water intake for ≥ 2 h. A 100mg dose of roxadustat was selected because it allowed for potential increases in exposure without any safety concerns based on findings from previous studies [13][14][15]. In addition, this dose level was considered sufficient for the evaluation of the concentrations of roxadustat and its metabolites.…”

Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF‐PH inhibitors

“…Treatment with HIF‐PHI is also associated with decreased blood ferritin level and hepcidin level 24,25 . Iron deficiency is associated with thromboembolic events, and clinical trials of roxadustat in Japan have reported increased incidence of thromboembolic events 26 . As treatment with HIF‐PHIs may decrease serum iron levels due to increased availability of iron for erythropoiesis, one should pay attention to avoid treatment‐induced reduction in serum iron levels.…”