HIF_prolyl-hydroxylase_inhibitor
Not to be confused with Factor Inhibiting HIF Asparaginyl Hydroxylase Inhibitors
Hypoxia-inducible factor prolyl hydroxylase Inhibitors (HIF-PHIs) also known as hypoxia-inducible factor stabilizers (HIF stabilizers) are a novel class of drugs that act by inhibiting hypoxia-inducible factor-proline dioxygenase (HIF prolyl-hydroxylase) which is responsible for breaking down the hypoxia-inducible factor (HIF) under conditions of normal oxygen concentrations.
As of 2023, Vadadustat, Daprodustat, and Roxadustat are the most studied HIF-PHIs with highest number of phase III & Phase IV patient data for chronic kidney disease.[1][2] All the three drug are available in Japan, while Vadadustat & Daprodustat is under EU regulatory review for potential approval in 2023. US FDA approved Daprodustat in early 2023 after a positive adcom for favorable benefit-risk ratio, while Vadadustat is awaiting an even-handed response to its formal dispute resolution appeal, considering recent FDA approval of Daprodustat.[3]
Outside of chronic kidney disease, Akebia Therapeutics has reported initial findings from its phase II study evaluating Vadadustat for ARDS in Covid-19 patients.[4] Based on the results Akebia Therapeutics has decided to move forward with a phase III study in broader ARDS patients.[5]
The rights to Vadadustat is held by Akebia Therapeutics in partnership with CSL Vifor, Roxadustat by Fibrogen in partnership with Astellas, and Daprodustat has been internally developed by GSK.[6][7]
