molecules of the month


oral HIF-PHD enzyme inhibitor

Ph. III candidate for anemia in CKD

carboxylic acid class of HIF-PHD inhibitors

J. Pharmacol. Exp. Ther.

Akebia Therapeutics, Cambridge, MA

Vadadustat chemical structure oral HIF-PHD enzyme inhibitor - Akebia Therapeutics, Cambridge, MA
4 mins read

Context. Vadadustat (Akebia Therapeutics) is an oral hypoxia-inducible factor prolyl-4-hydroxylase domain (HIF-PHD) inhibitor being developed for anemia in patients with chronic kidney disease (CKD). HIFs are transcription factors that mediate the expression of target genes, including for erythropoietin (EPO). In CKD, inhibition of PHDs, a trio of oxygenases, leads to stabilization of HIFs and erythropoiesis, reducing anemia, a significant complication of CKD. The observed effects of the drug on hemoglobin in the clinic, have led to the approval of vadadustat in Japan. However, similar to the previous frontline drug roxadustat  (AstraZeneca and FibroGen), FDA concerns about vadadustat’s safety have stymied its US approval. In a recent complete response letter, the FDA noted that the data provided do not support a…

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