Roxadustat, a China-First-in-Class Drug, Secures Second Global Indication for Non-Dialysis-Dependent CKD Anemia

Author: 1℃

On August 20, the world’s first new drug, Roxadustat (brand name: Evrenzo), jointly developed by FibroGen and AstraZeneca, was launched for the first time in China.^®）Securing the World’s Second Indication in China, i.e., non-dialysis chronic kidney disease-associated anemia (NDD-CKD).

Roxadustat is the world’s first oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). It was approved for marketing by the National Medical Products Administration on December 17, 2018, for the treatment of anemia in patients with chronic kidney disease (CKD) undergoing dialysis, including those receiving hemodialysis and peritoneal dialysis. Notably, Roxadustat represents a triple “first” innovation breakthrough: it is the first globally original drug with a novel mechanism of action to be initially approved in China.

Roxadustat’s indication development in China is ahead of the global pace,This indication for chronic kidney disease-related anemia in non-dialysis patients was also first approved in China.As of now, roxadustat is under marketing authorization review in Japan for the indication of anemia in patients with chronic kidney disease undergoing dialysis; marketing applications have not yet been submitted in Europe or the United States.

Roxadustat Rights Ownership:

Roxadustat was originally developed by FibroGen;

On April 28, 2006, FibroGen and Astellas Pharma entered into a collaborative development agreement for roxadustat, granting Astellas Pharma the rights to develop and commercialize the drug in Europe, the Commonwealth of Independent States (CIS), the Middle East, and South Africa.

On July 31, 2013, FibroGen and AstraZeneca entered into a collaboration agreement for the development of roxadustat, whereby the two parties would jointly develop roxadustat in the United States, China, and other regions worldwide excluding those specified in item 2.

In 2019, other noteworthy milestone events for roxadustat included:

In the third quarter of 2019, a marketing application will be submitted to the FDA for the indication of anemia in patients with chronic kidney disease (CKD) undergoing dialysis or non-dialysis-dependent CKD-related anemia (DD/NDD-CKD).

In 2019, a marketing authorization application will be submitted to the EMA for the indication of DD/NDD-CKD;

Expected to be officially launched in China in the third quarter of 2019;

This article primarily focuses on the key clinical trial FGCL-4592-808 (CTR20150609, NCT02652819) that supported the recent indication expansion of roxadustat, while also providing a brief overview of similar HIF-PH inhibitor products available in China.

I. Significant Clinical Benefits of Anemia Management in Patients with Chronic Kidney Disease on Dialysis

Roxadustat has three key clinical trials registered in China, summarized in the table below:

Among these, the clinical trial FGCL-4592-808 (CTR20150609, NCT02652819) provided the key data supporting this indication expansion, and the results have been published in The New England Journal of Medicine under the title “Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.”

Anemia is one of the common complications in patients with chronic kidney disease (CKD). A total of 154 patients were enrolled in study CTR20150609 to evaluate the efficacy and safety of roxadustat in treating anemia in non-dialysis-dependent CKD subjects.

DOI: 10.1056/NEJMoa1813599

Data shows:

Roxadustat vs. placebo, patient hemoglobin levels 1.9 ± 1.2 g/dL vs. -0.4 ± 0.8 g/dL;

Compared with placebo, roxadustat significantly increased (P<0.001) hemoglobin levels in patients, delivering significant clinical benefits to patients with chronic kidney disease not on dialysis!

II. Development of HIF-PH Inhibitors in China

Currently, there are over 100 million patients with chronic kidney disease (CKD) in China, among whom more than 1 million have end-stage renal disease (ESRD) and require dialysis or kidney transplantation. Anemia complicates 98.2% of dialysis-dependent patients and 52.1% of non-dialysis-dependent CKD patients. The mainstay of pharmacological treatment consists of iron supplements and erythropoiesis-stimulating agents (ESAs), both primarily administered via injection.

Upon reviewing available information, the author found that among domestic companies, HIF-PH inhibitors from Hengrui Medicine, Dongyangguang Pharmaceutical, and 3SBio are either in clinical trials or have just received Investigational New Drug (IND) approval. The key details are as follows:

Note: #The author speculates that the company has not yet issued an announcement

*http://www.zjhuanzi.com/uploadfile/upfiles/201903010927225c788a7a77667.pdf

Roxadustat has significant market potential. Clarivate previously predicted that the product’s sales would reach $2 billion in 2022, while EvaluatePharma analysts believe its peak sales could reach $5.8–8.1 billion. Currently, products under development by domestic companies remain in the early stages of clinical trials, warranting long-term attention to related product development.