FibroGen Submits NDA to U.S. FDA for Roxadustat to Treat Anemia in Chronic Kidney Disease Patients

Today, FibroGen, a partner of WuXi AppTec, announced that it has submitted a New Drug Application (NDA) to the U.S. FDA for roxadustat, a “first-in-class” hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) jointly developed with Astellas and AstraZeneca, for the treatment of anemia in dialysis and non-dialysis patients with chronic kidney disease (CKD). Previously, roxadustat was approved for marketing in China for the treatment of patients with anemia caused by CKD. Notably, the drug’s target, the “oxygen-sensing pathway,” was awarded the Nobel Prize this October.

Renal anemia is one of the major complications during the decompensated phase of renal function in chronic kidney disease (CKD). According to statistical data cited in a press release, the prevalence of CKD among the global adult population ranges from 10% to 12%. As CKD progresses, both the prevalence and severity of CKD-related anemia gradually increase. Patients with renal anemia often experience fatigue and have a poor quality of life. Both dialysis-dependent and non-dialysis-dependent CKD patients exhibit high morbidity and mortality rates. CKD can occur at any age but is more common in the elderly. Currently, the standard treatment for renal anemia involves erythropoiesis-stimulating agents (ESAs), such as alfaepoetin, combined with intravenous iron supplementation.

Roxadustat is an oral small-molecule hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for the treatment of renal anemia. The physiological role of hypoxia-inducible factor (HIF) not only increases erythropoietin expression but also upregulates the expression of erythropoietin receptors and proteins that promote iron absorption and circulation. Roxadustat inhibits prolyl hydroxylase (PH) by mimicking one of its substrates, alpha-ketoglutarate, thereby affecting the role of PH in maintaining the balance between HIF synthesis and degradation rates, ultimately achieving the correction of anemia.

▲Molecular structure of roxadustat (Image source: Meodipt [Public domain or Public domain], from Wikimedia Commons)

The submission of this new drug application is based on the positive results from a Phase 3 clinical development program comprising 15 clinical trials, which enrolled more than 10,000 patients globally. Previously, The New England Journal of Medicine (NEJM) published the positive results of roxadustat in two Phase 3 clinical trials. The trial results demonstrated that, compared with the standard therapy epoetin alfa, roxadustat showed no significant differences in clinical benefits and side effects for dialysis-dependent patients. For patients with renal anemia not undergoing dialysis, roxadustat delivered significant clinical efficacy, effectively correcting and maintaining hemoglobin levels. Additionally, FibroGen had previously announced positive results from five other Phase 3 trials of roxadustat. These data indicate that roxadustat provides clinical benefits for patients with chronic kidney disease (CKD), both dialysis-dependent and non-dialysis-dependent, compared with current standard therapies.

“Submitting this new drug application is an important step toward bringing roxadustat, a novel oral medication, to patients with anemia associated with chronic kidney disease (CKD) in the United States,” said Mr. Jim Schoeneck, Chief Executive Officer of FibroGen. “We look forward to continuing our collaboration with the FDA to make roxadustat available as soon as possible to dialysis and non-dialysis patients suffering from anemia due to chronic kidney disease.”

References:

[1] FibroGen Submits New Drug Application to the U.S. FDA for Roxadustat in Patients With Anemia of Chronic Kidney Disease, Retrieved December 23, 2019, from https://fibrogen.gcs-web.com/news-releases/news-release-details/fibrogen-submits-new-drug-application-us-fda-roxadustat-patients

[2] Express | A Milestone! Top Medical Journal Publishes Two Phase 3 Clinical Trial Results of Roxadustat, Retrieved December 23, 2019, from https://mp.weixin.qq.com/s/hf23U3IgRMThfJ259AxEPw

Flash | Targeting the Nobel Prize-winning signaling pathway! Roxadustat submits new drug application in the US

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