An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease

ABSTRACT

Introduction

Anemia is one of the major complications of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) have been the mainstay of renal anemia treatment. However, there are several safety drawbacks, and a safer and more effective alternative treatment has been sought.

Areas covered

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been developed as a novel orally active therapeutic agent for renal anemia. HIF-PHIs stimulate endogenous EPO and optimize iron utilization. Roxadustat is a first-in-class HIF-PHI for the treatment of anemia in CKD patients approved in China, Japan, South Korea, and Chile. The authors herein evaluate the pharmacology of roxadustat and give their expert perspectives on its use.

Expert opinion

Phase 3 clinical trials have demonstrated that roxadustat effectively increases and maintains hemoglobin (Hb) levels in both nondialysis-dependent and dialysis-dependent CKD patients. Roxadustat also improved iron metabolism and reduced intravenous (IV) iron requirements. However, pooled analyses of phase 3 studies have revealed frequent thromboembolic events in the roxadustat group, which might be attributed to rapid changes in Hb and inadequate iron supplementation. Roxadustat is an attractive alternative treatment especially for patients with ESA hyporesponsive due to impaired iron utilization, and so appropriate selection of target patients and its proper use are crucially important.

KEYWORDS:

• Anemia
• chronic kidney disease
• erythropoiesis-stimulating agents
• hypoxia-inducible factor
• hypoxia-inducible factor prolyl hydroxylase inhibitors
• roxadustat

Drug summary box

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Declaration of interest

M Nangaku has received research grants from the JT group and Kyowa Kirin Co. Ltd. He has also received personal fees from GlaxoSmithKline, Astellas, Mitsubishi Tanabe Pharma Corporation, Bayer Yakuhin Ltd, AstraZeneca and Torii Pharmaceutical Co. Ltd all outside the submitted work. T Tanaka has meanwhile received research grants from the JT group and Bayer as well as personal fees from Astellas, Kyowa Kirin Co. Ltd, Mitsubishi Tanabe and AstraZeneca. 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.

Additional information

Funding

This manuscript was not funded.