Positive results from two roxadustat Phase III trials in China for the treatment of anaemia published in The New England Journal of Medicine

AstraZeneca today announced that data from two Phase III trials evaluating the efficacy and safety of roxadustat in China have been published in The New England Journal of Medicine.

The trials, Study 806 and 808, evaluated roxadustat in Chinese patients with anaemia caused by chronic kidney disease (CKD) who are either dialysis-dependent (DD) or non-dialysis-dependent (NDD), respectively. In both trials, the primary efficacy endpoints were met. Results were previously presented at the American Society of Nephrology Kidney Week Annual Meeting in 2018.

In Study 806, DD-CKD patients with anaemia previously treated with erythropoiesis-stimulating agents (ESAs), the current standard of care for these patients, were randomised to receive roxadustat or epoetin alfa, an ESA, over 26 weeks. The trial met its primary efficacy endpoint of a mean change in haemoglobin (Hb) from baseline averaged over weeks 23-27 for patients treated with roxadustat compared to epoetin alfa. Roxadustat showed a numerically greater mean change in Hb in patients receiving roxadustat compared to epoetin alfa, showing it was statistically non-inferior. In a subgroup analysis of patients with inflammation marked by elevated c-reactive protein (CRP), roxadustat achieved consistent Hb control regardless of the patients' inflammation status, compared to epoetin alfa.

In Study 808, for the first eight weeks, NDD-CKD patients with anaemia were randomised to receive roxadustat or placebo. For the following 18 weeks, all patients were treated with roxadustat. The trial met its primary efficacy endpoint of mean change in Hb from baseline to weeks seven to nine. Patients randomised to roxadustat had a statistically significant greater mean change in Hb from baseline compared to patients randomised to placebo.

The safety profile of roxadustat in both studies was consistent with previous clinical trials of roxadustat in the CKD patient population.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “We are pleased that The New England Journal of Medicine has recognised the significance of the Phase III clinical trial programme in China for roxadustat. There are 120 million patients living with chronic kidney disease in China, a disease that is often associated with anaemia which can contribute to increased mortality. These trials demonstrate that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) like roxadustat may be able to more effectively address anaemia in CKD than the current standard of care, specifically in the Chinese patient population.”

AstraZeneca and FibroGen China, a wholly-owned subsidiary of FibroGen Inc., are collaborating on the development and commercialisation of roxadustat in China. Roxadustat is currently approved in China for the treatment of patients with anaemia in DD-CKD. The submission for NDD-CKD patients is under review by China’s National Medical Product Administration (NMPA).

About roxadustat

Roxadustat is a first-in-class, orally-administered small-molecule medicine recently approved in China for the treatment of dialysis-dependent patients with anaemia from CKD. Roxadustat is a 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. Administration 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 at maintenance doses typically required in CKD. Additionally, roxadustat is effective in multiple subpopulations of CKD patients, including those with inflammation, and generally without a need for supplemental intravenous (IV) iron.

AstraZeneca and FibroGen China are collaborating on the development and commercialisation of roxadustat in China. FibroGen China, based in Beijing, is a wholly-owned subsidiary of FibroGen Inc. that sponsored the development and registration of roxadustat. FibroGen China conducted the China Phase III clinical trials and submitted the New Drug Application for registration of roxadustat to the Chinese regulatory authorities. Following this approval, AstraZeneca will manage commercialisation activities in China, and FibroGen China will manage commercial manufacturing and medical affairs as well as continued clinical development and regulatory affairs. AstraZeneca and FibroGen expect to launch roxadustat in China during the second half of 2019.

About anaemia in CKD in China

Anaemia commonly develops in association with CKD and is linked to significant morbidity and mortality in both the dialysis and non-dialysis populations. CKD affects an estimated 120 million patients in China.² Although CKD may occur at any age, it is more common in aging populations, and its prevalence is increasing. CKD can be both a cause and a consequence of cardiovascular disease and is a critical healthcare issue. There is no treatment available that is curative or has the ability to stop kidney deterioration.

About AstraZeneca in CVRM

Cardiovascular, renal and metabolism (CVRM) together form one of AstraZeneca’s three therapy areas and are a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling comorbidities. Our ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.

References

1.     Babitt JL, Lin HY. Mechanisms of Anemia in CKD. J Am Soc Nephrol (2012); 23:1631-1634.

2.     Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 2012; 379: 815–22.