Phase 3 data on roxadustat show promise in treating anaemia in CKD patients

November 16, 2019 0 By FM

Roxadustat significantly increased the haemoglobin levels in patients suffering with anemia from chronic kidney disease, reveals data from the phase 3 studies.

The results from the trial were presented by AstraZeneca at the American Society of Nephrology (ASN) Kidney Week 2019 held in Washington on 8th November.

Anaemia due to kidney disease is commonly associated with significant morbidity and death. It is mainly caused by a decrease in erythropoietin (EPO) hormone production in the kidneys. EPO is responsible for red blood cell maturation in the bone marrow.

Recombinant human erythropoietin (epoetin alfa) was used as an erythropoietin stimulating agent in treating anaemia due to CKD which had become the standard of care for the treatment. However, some studies have disclosed that using ESAs to target normal haemoglobin levels may be harmful and need to follow strict guidelines to keep haemoglobin levels within the recommended range .

Roxadustat, an oral first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is claimed to promote erythropoiesis by increasing endogenous production of EPO and improving iron regulation.

The drug overcomes the negative impact of inflammation on haemoglobin synthesis and red blood cell production by downregulating hepcidin inducing coordinated erythropoiesis.

The global phase 3 programme was collaboratively conducted by AstraZeneca, FibroGen and Astellas and consisted of seven trials in more than 9,000 patients.

The results from phase 3 OLYMPUS trial reported a mean increase of 1.75g/dL in Hb levels compared to 0.40g/dL as observed with placebo in 28 to 52 weeks. The trial evaluated the safety and efficacy of roxadustat versus placebo in 2781 patients with anaemia suffering from non-dialysis dependent (NDD) CKD.

The results from the ROCKIES trial which evaluated roxadustat vs epoetin alfa demonstrated a significant mean increase in Hb (0.77g/dL) in over 28 to 52 weeks compared to a mean rise of 0.68g/dL with epoetin alfa. The trial had evaluated 2,133 dialysis-dependent (DD)-CKD patients with anaemia.

Also patients treated with roxadustat required less monthly administration of intravenous (IV) iron (mean=59mg) compared to those treated with epoetin alfa (mean=91mg)from week 36 onwards, reported the researchers.

The drug also improved Hb levels in patients with elevated high sensitivity C-reactive proteins which is an indicator of inflammation, regardless of treatment with placebo or epoeitin alfa.

The cardiovascular safety analysis presented at the event by AZ and FibroGen based on pooled trials receiving roxadustat reported no risk of major adverse CV events in NDD-CKD patients compared to placebo and DD-CKD patients compared to epoetin alfa treatment.

Roxadustat is currently approved in China for the treatment of anaemia in patients with dialysis-dependent and non-dialysis dependent CKD, and in Japan for the treatment of dialysis patients with anaemia from CKD.