title: 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.
abstract: 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.
  
  
  METHODS
  Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study.
  
  
  METHODS
  Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  METHODS
  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<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised.
  
  
  CONCLUSIONS
  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.
authors: St. John Hospital & Medical Center, Detroit, MI.
authors: Robert
authors: R
authors: Provenzano
authors: FibroGen, Inc, San Francisco, CA.
authors: Anatole
authors: A
authors: Besarab
authors: US Renal Care, Pine Bluff, AR.
authors: Steven
authors: S
authors: Wright
authors: Valley Renal Medical Group, Northridge, CA.
authors: Sohan
authors: S
authors: Dua
authors: Pines Clinical Research, Pembroke Pines, FL.
authors: Steven
authors: S
authors: Zeig
authors: US Renal Care, Ft Worth, TX.
authors: Peter
authors: P
authors: Nguyen
authors: FibroGen, Inc, San Francisco, CA.
authors: Lona
authors: L
authors: Poole
authors: FibroGen, Inc, San Francisco, CA.
authors: Khalil G
authors: KG
authors: Saikali
authors: FibroGen, Inc, San Francisco, CA.
authors: Gopal
authors: G
authors: Saha
authors: FibroGen, Inc, San Francisco, CA.
authors: Stefan
authors: S
authors: Hemmerich
authors: FibroGen, Inc, San Francisco, CA.
authors: Lynda
authors: L
authors: Szczech
authors: FibroGen, Inc, San Francisco, CA. Electronic address: pyu@fibrogen.com.
authors: K H Peony
authors: KH
authors: Yu
authors: FibroGen, Inc, San Francisco, CA.
authors: Thomas B
authors: TB
authors: Neff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy*; D000068817:Epoetin Alfa / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006397:Hematinics; D007546:Isoquinolines; D000068817:Epoetin Alfa; D005998:Glycine; C584543:roxadustat
keywords: Hb correction; Hb maintenance; Hb response; Hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI); anemia; chronic kidney disease (CKD); dialysis; end-stage renal disease (ESRD); erythropoiesis; erythropoietin; hemoglobin (Hb); hepcidin; iron transport; randomized trial; roxadustat