Roxadustat: First Global Approval

Drugs. 2019 Apr;79(5):563-572. doi: 10.1007/s40265-019-01077-1.


Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. Inhibition of these enzymes reduces HIF breakdown and promotes HIF activity, leading to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability and increases haemoglobin levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism. Roxadustat is approved in China and is under regulatory review in Japan for the treatment of anaemia in patients with dialysis-dependent CKD. Studies are underway to investigate long-term cardiovascular outcomes with roxadustat versus placebo (for non-dialysis-dependent CKD) or standard of care (for dialysis-dependent CKD). This article summarizes the milestones in the development of roxadustat leading to this first approval.

Publication types

  • Review

MeSH terms

  • Anemia / drug therapy*
  • Anemia / metabolism
  • China
  • Drug Approval
  • Erythropoiesis / drug effects
  • Erythropoietin / metabolism
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / pharmacokinetics
  • Glycine / therapeutic use
  • Hepcidins / metabolism
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / adverse effects
  • Isoquinolines / pharmacokinetics*
  • Isoquinolines / therapeutic use
  • Prolyl-Hydroxylase Inhibitors / administration & dosage
  • Prolyl-Hydroxylase Inhibitors / adverse effects
  • Prolyl-Hydroxylase Inhibitors / pharmacokinetics*
  • Prolyl-Hydroxylase Inhibitors / therapeutic use
  • Renal Dialysis


  • Hepcidins
  • Isoquinolines
  • Prolyl-Hydroxylase Inhibitors
  • Erythropoietin
  • Glycine
  • roxadustat