Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study

Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Study Design Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Setting & Participants Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Intervention Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Outcomes Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of −0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Measurements Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Results Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm ( P =0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa ( P Limitations Short treatment duration and small sample size. Conclusions In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.