Roxadustat

Roxadustat is an oral medicine that inhibits hypoxia-inducible factor prolyl hydroxylase (HIF-PHI), and it may help treat anaemia. Once taken, it binds to HIF-PH and blocks it. This enzyme normally breaks down the transcription factors of the HIF family when oxygen levels are normal. With the enzyme blocked, HIF isn't broken down and its activity rises. More HIF activity means the body makes more of its own erythropoietin, and red blood cell production goes up. Roxadustat also lowers the expression of the peptide hormone hepcidin, improves iron availability and raises haemoglobin (Hb) levels. HIF controls the expression of genes in response to low oxygen, including the genes needed for erythropoiesis and iron metabolism. In several subgroups of CKD patients, roxadustat has been shown to produce coordinated erythropoiesis and raise the red blood cell count, while plasma erythropoietin stays within or near the normal physiologic range. This held true even when inflammation was present, and without any need for extra intravenous iron.

Roxadustat binds reversibly to the HIF prolyl hydroxylase enzymes and inhibits them potently. This reduces the breakdown of HIF-α and promotes HIF transcriptional activity. When the HIF pathway is switched on this way, the target genes involved in erythropoiesis are induced, such as those for EPO, the EPO receptor, and the proteins that promote iron absorption, iron transport and haem synthesis. In patients with anaemia of CKD who were not dependent on dialysis, roxadustat raised haemoglobin (Hb) levels in a dose-dependent way, significantly reduced hepcidin levels, and briefly raised endogenous EPO levels within or near the physiological range. In patients with anaemia linked to dialysis-dependent or dialysis-independent CKD, roxadustat reduced the disturbance of iron metabolism that comes with CKD. It did this by increasing serum transferrin, intestinal iron absorption and the release of stored iron, all in a dose-dependent manner. Cholesterol levels also fell significantly from baseline with roxadustat, whether or not the patient was using statins or other lipid-lowering agents.