Roxadustat in the treatment of anaemia in chronic kidney disease

ABSTRACT

Introduction: Anaemia is one of the hallmarks of advanced chronic kidney disease (CKD); it correlates with a lower quality of life and increased cardiovascular risk. Currently its management is based on iron and erythropoiesis-stimulating agents (ESAs) therapy. Given safety issues on ESA therapy and excessive iron use, anaemia management is still suboptimal.

Areas covered: The inhibitors of the prolyl-hydroxylases domain (PHD) are oral drugs which activate the hypoxia-inducible factors (HIF) and stimulate the production of endogenous erythropoietin. Roxadustat (FG-4592) is a second-generation PHD inhibitor; it is undergoing now phase-III clinical development.

Expert opinion: Phase-II clinical trials have shown that roxadustat is effective and save in the short term in either non-dialysis or dialysis CKD patients. Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies.

KEYWORDS:

• Anaemia
• chronic kidney disease
• erythropoiesis stimulating agents
• HIF
• hepcidin
• prolyl-hydroxylases domain
• roxadustat

Box 1. Drug summary box

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Declaration of interest

L. Del Vecchio has served on advisory boards for Astellas and received speakers fees from Roche. F. Locatelli is or was a member of advisory board for Akebia, Amgen and Astellas. He has also been a speaker at symposia supported by Amgen, Astra Zeneca, Fibrogen, Roche, Vifor Fresenius Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

One peer reviewer declares that they have served on an advisory board for Akebia (producer of vadadustat) and received editorial assistance funded by AstraZeneca (sponsor of roxadustat) in the development of a manuscript they co-authored on HIF-PHIs (published in June 2017).

Additional information

Funding

This paper was not funded.