ATC Group: B03XA Other antianemic preparations

Daprodustat is indicated for the treatment of anemia due to chronic kidney disease. Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC₅₀ in the low nM range). This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin.

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as the endogenous hormone. Darbepoetin alfa has five N-linked carbohydrate chains whereas the endogenous hormone and recombinant human erythropoietins (r-HuEPO) have three. The additional sugar residues are molecularly indistinct from those on the endogenous hormone. Due to its increased carbohydrate content darbepoetin alfa has a longer terminal half-life than r-HuEPO and consequently a greater in vivo activity.

Epoetin alfa is a glycoprotein hormone produced primarily by the kidney in response to hypoxia and is the key regulator of red blood cell (RBC) production. Epoetin alfa is involved in all phases of erythroid development, and has its principal effect at the level of erythroid precursors.

Epoetin beta stimulates erythropoiesis by interaction with the erythropoietin receptor on progenitor cells in the bone marrow. Epoetin beta is a continuous erythropoietin receptor activator that shows a different activity at the receptor level characterized by a slower association to and faster dissociation from the receptor, a reduced specific activity in vitro with an increased activity in vivo, as well as an increased half-life, in contrast to erythropoietin.

Epoetin theta is identical in its amino acid sequence and similar in its carbohydrate composition (glycosylation) to endogenous human erythropoietin. After administration of epoetin theta, the number of erythrocytes, the haematocrit values and reticulocyte counts increase.

Epoetin zeta is a recombinant human erythropoietin. Erythropoietin (EPO) is a glycoprotein hormone produced primarily by the kidney in response to hypoxia and is the key regulator of red blood cell (RBC) production. The 2 are indistinguishable on the basis of functional assays.

Luspatercept, an erythroid maturation agent, is a recombinant fusion protein that binds selected transforming growth factor-β (TGF-β) superfamily ligands. By binding to specific endogenous ligands (e.g. GDF-11, activin B) luspatercept inhibits Smad2/3 signalling, resulting in erythroid maturation through differentiation of late-stage erythroid precursors (normoblasts) in the bone marrow.

Roxadustat is a hypoxia-inducible factor, prolyl hydroxylase inhibitor (HIF-PHI). The activity of HIF-PH enzymes controls intracellular levels of HIF, a transcription factor that regulates the expression of genes involved in erythropoiesis. Activation of the HIF pathway is important in the adaptative response to hypoxia to increase red blood cell production.

Vadadustat is a hypoxia-inducible factor prolyl-hydroxylase inhibitor which leads to increased cellular levels of hypoxia-inducible factor thereby stimulating endogenous erythropoietin (EPO) production, increasing iron mobilization and red blood cell production, resulting in gradual rate of rise in Hb.