Roxadustat Marks a Milestone: NEJM Publishes Two Pivotal Phase III Studies from China Back-to-Back

In the early hours of July 25, 2019, Beijing time, the world's topMedicineThe New England Journal of Medicine (NEJM) published back-to-back online articles presenting two studies on roxadustat, an innovative drug for renal anemia, announcing the results of its two Phase III clinical trials in China; accompanied by commentaries from internationally renowned nephrology experts.

This marks the first time NEJM has published a Phase III clinical trial of a new drug with physicians from mainland China as both the first and corresponding authors, and also the first time the journal has published back-to-back clinical trials from Chinese research teams.

Roxadustat, a Class 1 innovative drug in China and the world’s first oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), was first launched in China on December 17, 2018, for the treatment of renal anemia in dialysis patients. The release of Phase III clinical trial data on roxadustat marks a significant milestone in the field of nephrology in China.

On August 6, a media roundtable for in-depth interpretation of the clinical study data of roxadustat in China was held in Shanghai. The lead investigator of the Chinese clinical studies on roxadustat,Professor Chen Nan from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Professor Hao Chuanming from Huashan Hospital, Fudan University, and Mr. Zhao Jianfei, Deputy Editor-in-Chief of NEJM Medical FrontiersAttended the event and shared the story behind roxadustat with multiple well-known media outlets.

Roxadustat: Bringing New Hope for Life to Patients with Kidney Disease

Chronic kidney disease (CKD) is the most prevalent major chronic disease in China, following cardiovascular and cerebrovascular diseases and diabetes. With a prevalence rate of 10.8%, CKD imposes a substantial healthcare burden on China, given its large population base. As a significant complication of CKD, anemia poses severe health risks; it can accelerate the progression of CKD, increase the incidence of cardiovascular and cerebrovascular events and the risk of mortality, and seriously impair patients' quality of life. Currently, the treatment target attainment rate for renal anemia in China is very low. Available therapeutic agents are scarce, and their efficacy and safety profiles are unsatisfactory. In light of these unmet clinical needs, there is an urgent need to develop novel therapies for renal anemia with new mechanisms of action. It is against this backdrop that the HIF-PHI roxadustat has emerged.

Professor Nan Chen

Professor Chen Nan first presented the Phase III clinical trial results of roxadustat. This Class 1.1 new drug, developed in China through a collaboration between AstraZeneca and FibroGen, saw the release of its Chinese data as the first among global Phase III clinical trials. Two Phase III multicenter, randomized, double-blind, controlled clinical studies of roxadustat were conducted in China, targeting dialysis-dependent and non-dialysis-dependent patients, with erythropoietin (EPO) and placebo serving as the respective comparators. Both studies met their primary endpoints.

The results showed that roxadustat effectively corrected and maintained hemoglobin (Hb) levels in dialysis patients who had previously received erythropoietin (EPO) therapy, with no new or unexpected adverse reactions observed. In Chinese patients with chronic kidney disease (CKD) and anemia who were not undergoing dialysis, roxadustat was also found to effectively correct and maintain Hb levels, demonstrating a favorable safety profile.

Professor Hao Chuanming

Professor Hao Chuanming pointed out that the development of roxadustat originated from the discovery of hypoxia-inducible factor (HIF), an achievement that was awarded the Lasker Award, known as a bellwether for the Nobel Prize. Roxadustat promotes endogenous erythropoietin (EPO) production and improves iron absorption by inhibiting prolyl hydroxylase in the HIF pathway (HIF-PHI), thereby reducing hepcidin levels and effectively stimulating erythropoiesis.

He emphasized that the several key characteristics of roxadustat determine its broad clinical application prospects. First, its efficacy is not affected by inflammation; in chronic kidney disease, particularly during the uremic stage, various inflammatory responses are present in the body, yet roxadustat remains effective under inflammatory conditions. Second, it does not require concurrent intravenous iron supplementation. Third, as an oral formulation unaffected by food intake, it significantly improves treatment adherence. Fourth, it has a favorable safety profile, with no serious drug-related adverse events reported to date. Both professors expressed that they “have full confidence in roxadustat,” repeatedly emphasizing that its launch in China has brought new therapeutic hope to them as nephrologists and hope for life to patients with kidney disease.

Reflections Behind Successfully Publishing in Top-Tier Journals

Professor Chen Nan stated that since the paper was published online in the NEJM, she has received congratulations from various quarters both within China and around the world, with her social media feeds being flooded with messages. Reflecting on her journey in clinical research, she candidly acknowledged the numerous challenges faced and the multiple inspections conducted by regulatory authorities. She attributed the ultimate success to a combination of factors: first, the study featured an excellent top-level design; second, the team collaborated with great cohesion, with all participants striving to thoroughly understand and strictly adhere to the principles of Good Clinical Practice (GCP).

Meanwhile, with the growing public awareness of health, an increasing number of patients have come to understand and willingly participate in clinical trials. Pharmaceutical R&D companies have also provided strong support during the clinical research phase by deploying highly competent CRO teams for quality monitoring. It is through the concerted efforts of all parties involved that we now celebrate this success.

Professor Hao Chuanming further emphasized that despite the rapid development of medical science popularization in recent years, public understanding of chronic kidney disease (CKD) still lags far behind that of cancer. The publication of roxadustat’s clinical studies in top-tier journals presents a valuable opportunity to advance public awareness and improve the recognition of kidney diseases.

For scientists who relentlessly pursue progress, success signifies a new beginning. The two professors revealed that the market launch of roxadustat has broken the 30-year bottleneck in the field of renal anemia, during which no therapies with novel mechanisms were introduced. It has also opened up new perspectives for drug development in other fields based on the HIF pathway, providing a significant impetus to the overall advancement of the industry. It is reported that explorations into the application of roxadustat in other diseases, such as autoimmune anemia and myeloma, are currently underway. “The road ahead is long, and we will continue to strive harder.”

Roxadustat Illuminates a New Journey for Clinical Research in China

Deputy Editor-in-Chief Zhao Jianfei enthusiastically pointed out that the publication of two studies on roxadustat in the NEJM represents high recognition from the international medical community regarding the significance of this research, as well as the level and quality of clinical research conducted by the Chinese team. Being published online in a top-tier journal means that the study is first—the earliest of its kind—as it marks the first international study on a new drug targeting the HIF pathway, and also the first time a new drug clinical study has been completed by China internationally. At the same time, it is the best, indicating that the research has reached an exceptionally high standard of clinical investigation with very high data quality. This is the first time that clinical research on a new drug from China has received such high-level recognition from international peers, which is truly commendable.

Deputy Editor-in-Chief Zhao Jianfei

He emphasized that in recent years, China has made significant progress in the clinical research of new drugs. The surge in clinical study submissions from China received by the New England Journal of Medicine (NEJM), along with the increasing number of new drugs submitted for approval and approved annually, indicates that China’s new drug development is entering a period of explosive growth. In 2017, China joined the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), marking the alignment of China’s drug clinical research and related standards with global practices. It is believed that more high-quality clinical studies from China will be published in top-tier journals, including NEJM, in the future.

So, what are the main bottlenecks currently facing clinical research in China? Professor Chen Nan stated bluntly that there is still a significant shortage of personnel dedicated to clinical research. She called for clinicians to gain a deeper understanding of the importance of clinical research and emphasized the need to cultivate more teams across China capable of conducting clinical studies in strict adherence to Good Clinical Practice (GCP) principles. Meanwhile, it is essential to establish and improve clinical research-related institutions, including ethics committees, at hospitals of all levels. Additionally, governments at all levels should establish and strengthen relevant oversight bodies to closely monitor clinical research data.

As the world’s first HIF-PHI, Roxadustat has achieved three groundbreaking “firsts”: it is the first globally novel drug; its Phase III clinical trial, with mainland Chinese physicians serving as both first and corresponding authors, was published in the New England Journal of Medicine (NEJM) for the first time; and two clinical trials by Chinese research teams were published back-to-back in NEJM for the first time. This accomplishment is a source of pride not only for China’s broad community of clinical research scientists but also for the Chinese nephrology field. Amid this joy, we look forward to seeing more new drugs and innovative studies showcased on the international academic stage, thereby broadening the path of independent innovation with Chinese characteristics and accelerating the realization of the Healthy China vision.