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Roxadustat for treating symptomatic anaemia in chronic kidney disease

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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NICE state that roxadustat is recommended as an option for treating symptomatic anaemia associated with chronic kidney disease (CKD) in adults only if:

  • they have stage 3 to 5 CKD with no iron deficiency and
  • they are not on dialysis at the start of treatment and
  • the company provides roxadustat according to the commercial arrangement

The NICE committee noted that:

  • "..Treatment for symptomatic anaemia associated with chronic kidney disease includes erythropoiesis stimulating agents (ESAs). Roxadustat is an alternative to ESAs. A clinical trial comparing roxadustat with darbepoetin alfa (an ESA) shows that roxadustat works as well as darbepoetin alfa .."

Hypoxia-inducible factor (HIF) proteins

  • under physiological conditions, the HIF proteins are inactivated by enzymes of the prolyl hydroxylase domain (PHD), by targeting HIF proteins for degradation
  • for the condition of hypoxia, the PHD enzymes are downregulated and the HIF proteins stay high
    • HIF proteins stimulate the erythropoietin (EPO) gene in kidney parenchymal cells to produce EPO, as well as other genes, including the iron transporter ferroportin
      • EPO activates red blood cell (RBC) production in bone marrow, and ferroportin facilitates iron absorption in the small intestine

Roxadustat

  • is an orally administered small molecule drug that prevents the enzymatic degradation of HIF-1alpha by inhibiting the PHD enzymes
  • causes the hematocrit rises and hemoglobin concentrations to increase

Reference:

  1. NICE (July 2022). Roxadustat for treating symptomatic anaemia in chronic kidney disease
  2. Czock D, Keller F. Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat. Clin Pharmacokinet. 2022 Mar;61(3):347-362.

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