Roxadustat for treating symptomatic anaemia in chronic kidney disease

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.