AstraZeneca CKD anaemia drug Roxadustat shows increased haemoglobin levels in Phase 3 trial

New Delhi: AstraZeneca recently presented detailed results from the Phase III OLYMPUS and ROCKIES trials showing that Roxadustat significantly increased haemoglobin (Hb) levels in non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anaemia from chronic kidney disease (CKD), respectively.

Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that promotes erythropoiesis by increasing endogenous production of erythropoietin and improving iron regulation and overcoming the negative impact of inflammation on haemoglobin synthesis and red blood cell production by downregulating hepcidin. Use of Roxadustat has been shown to induce coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range, in multiple subpopulations of CKD patients, including in the presence of inflammation and without a need for supplemental IV iron.

Roxadustat is currently approved in China for the treatment of anaemia in patients with CKD, regardless of whether they require dialysis. Data from the Phase III OLYMPUS and ROCKIES trials, together with the efficacy and pooled CV safety data from the global Phase III programme, will form part of the regulatory submission in the US, anticipated in Q4 2019.

The OLYMPUS trial compared Roxadustat to placebo while the ROCKIES trial compared Roxadustat to epoetin alfa. The results were presented today during two oral sessions at the American Society of Nephrology (ASN) Kidney Week 2019 in Washington, D.C., US.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "Anaemia is a common, serious condition among patients with chronic kidney disease. It occurs when the body has fewer healthy red blood cells than normal and low levels of haemoglobin, which may leave patients fatigued and short of breath. Results from OLYMPUS and ROCKIES reinforce the potential role that Roxadustat could play in increasing haemoglobin levels and managing anaemia, which is often underdiagnosed and undertreated."

Steven Fishbane, MD, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, US and primary investigator on the OLYMPUS and ROCKIES trials, said: "These data demonstrated that Roxadustat effectively increased haemoglobin levels for patients with anaemia from chronic kidney disease, including those who show signs of inflammation. Patients who experience chronic inflammation are often more difficult to treat than the overall chronic kidney disease patient population, emphasising the need for new treatment options."

In the OLYMPUS trial, Roxadustat demonstrated a statistically significant improvement in Hb levels from baseline, with a mean increase of 1.75g/dL averaged over weeks 28 to 52, compared to 0.40g/dL with placebo, the primary efficacy endpoint.

Roxadustat also improved Hb levels from baseline in a subgroup of patients with elevated high-sensitivity C-reactive protein (hsCRP) levels of greater than 5mg/L, with a statistically significant mean increase of 1.73 g/dL, compared to 0.62g/dL with placebo, a secondary endpoint. hs CRP is a protein in the blood that increases when inflammation is present.

Overall safety findings are generally consistent with the NDD-CKD patient population. For all patients, the most frequently reported adverse events in the intent to treat analysis set were the end-stage renal disease, pneumonia, urinary tract infection and hypertension. Additional serious adverse events reported were azotaemia, sepsis, acute kidney injury and hyperkalaemia.

In the ROCKIES trial, Roxadustat demonstrated a statistically significant improvement in Hb levels from baseline with a mean increase of 0.77g/dL averaged over weeks 28 to 52, compared to 0.68g/dL with epoetin alfa, the primary efficacy endpoint.

Roxadustat also improved Hb levels from baseline in a subgroup of patients with elevated hsCRP levels of greater than 5 mg/L, demonstrating a statistically significant improvement with a mean increase of 0.80g/dL compared to 0.59g/dL with epoetin alfa, a secondary endpoint. Patients treated with Roxadustat used less monthly intravenous (IV) iron (mean = 59mg) compared to those treated with epoetin alfa (mean = 91mg) from week 36 to the end of the study.

Adverse events with Roxadustat were generally similar to those seen in patients treated with epoetin alfa and commonly found in DD-CKD patients. In Roxadustat treated patients, the most frequently reported adverse events were diarrhoea, hypertension, pneumonia, headache and arteriovenous fistula thrombosis. Additional serious adverse events reported were sepsis and acute myocardial infarction.

Cardiovascular (CV) safety data from these trials will be reported as part of the pooled efficacy and CV safety analyses of DD-CKD and NDD-CKD patients from the global Phase III programme, which is being presented in the oral late-breaking abstract session "High-Impact Clinical Trials" at ASN Kidney Week on 8 November 2019.

Read Also: AstraZeneca gets marketing authorization for Roxadustat in China to treat anaemia caused by CKD