Current and future chemical therapies for treating anaemia in chronic kidney disease

ABSTRACT

Introduction: Erythropoiesis-stimulating agents (ESAs) are not perfect, since they have potential side effects. Iron therapy is also receiving growing attention in recent years.

Areas covered: We performed a literature search on PubMed using the following key words: anemia, chronic kidney disease, HIF stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders, iron dialysate. We reviewed new drugs that are under clinical development to obtain better safety and activity and/or easier and cheaper manufacturing processes in comparison to available ESAs. We also considered new strategies to increase iron stores.

Several phase 1 and 2 studies support the beneficial role of increasing Hypoxia Inducible factor (HIF) activity for stimulating endogenous erythropoiesis. Sotatercept and luspatercept, two activin traps, are undergoing clinical development mainly for indications other than CKD. They have the additional effect of improving osteoporosis. Iron-containing phosphate binders have become available recently.

Expert opinion: Several medical needs are unmet with ESA. HIF stabilisers are the most appealing drugs undergoing clinical development. They expose patients to lower levels of EPO than ESA, possibly reducing unintended effects. Their long-term safety is still to be demonstrated. One new iron-containing phosphate binders has the potential of combining two indications: hyperphosphoremia and iron deficiency, possibly improving compliance.

KEYWORDS:

• Chronic kidney disease
• renal anemia
• erythropoiesis stimulating agents
• dialysis
• HIF
• chronic renal insufficiency

Article highlights

• ESAs have been shown effective in correcting anaemia in the majority of CKD patients. Despite an acceptable safety profile, potential risks have been suggested.

• HIFs increase endogenous EPO synthesis by inhibiting the prolyl hydroxylase enzymes.

• HIFs are well tolerated and orally administered. They have been associated with a reduction of hepcidin levels and improved iron utilisation. Long-term studies to prove their safety are ongoing.

• Sotatercept is an activin traps capable of treating simultaneously anaemia and osteoporosis.

• Iron based phosphate binders may represent alternative approach to intravenous iron administration.

• Anti-hepcidin drugs increase iron availability.

This box summarizes key points contained in the article.

Declaration of interest

F Locatelli is or was a member of an advisory board of Akebia, Amgen, Astellas and he was speaker at meetings supported by Amgen, Astellas, Janssen, Roche and Vifor-Fresenius Pharma. L Del Vecchio has served on an advisory board of Astellas. 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 paper was not funded.