Roxadustat for CKD-related Anemia in Non-dialysis Patients

• Published in: Kidney international reports 2021-03, Vol.6 (3), p.624-635
• Main Authors: Coyne, Daniel W., Roger, Simon D., Shin, Sug Kyun, Kim, Sung Gyun, Cadena, Andres A., Moustafa, Moustafa A., Chan, Tak Mao, Besarab, Anatole, Chou, Willis, Bradley, Charles, Eyassu, Meraf, Leong, Robert, Lee, Tyson T., Saikali, Khalil G., Szczech, Lynda, Yu, Kin-Hung P.
• Format: Article
• Language: English
• Subjects: anemia; chronic kidney disease; Clinical Research; rescue therapy; roxadustat
• ISSN: 2468-0249; 2468-0249
• DOI: 10.1016/j.ekir.2020.11.034

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis. ANDES was a global Phase 3 randomized study in which adults with stage 3–5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28–52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline >8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded. In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28–52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74–1.97; P < 0.0001). The proportion of patients achieving a response at week 24 was larger for roxadustat (86.0%; 95% CI 83.0%–88.7%) versus placebo (6.6%; 95% CI 4.1%–9.9%; P < 0.0001). The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14–0.28; P < .0001). The incidences of TEAEs and TESAEs were comparable. This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190). [Display omitted]