Roxadustat Achieves Positive Results in Two Phase III Clinical Trials in China for the Treatment of Anemia in Chronic Kidney Disease

Compiled by: Li Jierui

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On July 25, AstraZeneca announced that two Phase III clinical trials of its anemia drug for chronic kidney disease, Roxadustat, conducted in China, had achieved positive results, demonstrating the drug’s favorable efficacy and safety profile.

The two trials, coded 806 and 808, evaluated the efficacy of roxadustat in Chinese patients with anemia due to chronic kidney disease (CKD), who were either dialysis-dependent (DD) or non-dialysis-dependent (NDD). Data from both trials were published in The New England Journal of Medicine. The results showed that roxadustat met the primary endpoint of improving hemoglobin (Hb) levels. Compared with epoetin alfa treatment, roxadustat extended the time to improvement by 23 to 27 weeks beyond the mean baseline value, indicating statistically significant efficacy.

In the analysis of the subgroup of inflammatory patients with elevated C-reactive protein (CRP), roxadustat achieved stable control of hemoglobin levels regardless of the patients' inflammatory status, comparable to epoetin alfa. Furthermore, the safety profile of roxadustat in the two studies was consistent with that previously observed in clinical trials.

Currently, FibroGen is collaborating with AstraZeneca to develop and commercialize roxadustat in the United States, China, and other markets for the treatment of anemia associated with chronic kidney disease. Meanwhile, FibroGen is also partnering with Astellas Pharma to address anemia in patients with chronic kidney disease and myelodysplastic syndromes in regions including Europe, the Middle East, and South Africa.

Molecular Structure of Roxadustat

Roxadustat is a first-in-class hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that not only increases erythropoietin expression but also upregulates the expression of erythropoietin receptors and proteins involved in iron absorption and circulation.

Mene Pangalos, Executive Vice President of Research and Development at AstraZeneca, stated, “These trials indicate that HIF-PH inhibitors may treat anemia associated with chronic kidney disease more effectively than the current standard of care, particularly in the Chinese patient population. China has approximately 120 million patients with chronic kidney disease, including over 400,000 undergoing dialysis, a number that is growing rapidly at a double-digit rate, thereby driving increasing demand for anti-anemia therapies. Roxadustat will provide a new treatment option for patients with anemia associated with chronic kidney disease in China.”

In December 2018, roxadustat became the first drug worldwide to receive approval from Chinese regulators for the treatment of anemia in dialysis-dependent patients with chronic kidney disease, and it is expected to be launched in China in the second half of this year. External forecasts predict that the drug’s sales could reach $1.97 billion by 2023. Currently, roxadustat is also undergoing regulatory review in Japan, with a plan to submit an application in the United States in the third quarter.

However, the future development of roxadustat is not without concerns, as it faces competition from other HIF-PH inhibitors under development, including vadadustat from Akebia Therapeutics and Mitsubishi Tanabe Pharma, and daprodustat from GlaxoSmithKline. Daprodustat is expected to be submitted for approval in Japan in 2019, and in the United States and Europe in 2020; vadadustat is also anticipated to have marketing applications filed within the year in the United States, the European Union, and Japan.

Reference source: AZ’s roxadustat successful in late-stage trial