roxadustat for treating symptomatic anaemia in chronic kidney disease

Last edited 07/2022 and last reviewed 10/2022

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.