FibroGen and AstraZeneca's Evrenzo (Roxadustat) Enters U.S. Regulatory Review as First-in-Class Oral HIF-PH Inhibitor for CKD-Related Anemia
Feb 12, 2020 19:17
CST Updated
19:17
AstraZeneca
Biopharmaceutical Manufacturer
FDA
U.S. Food and Drug Administration
February 12, 2020 /BioValleyBIOON/ -- FibroGen recently announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for Evrenzo (Chinese brand name: Airuizhuo; generic name: roxadustat), a drug indicated for the treatment of chronic kidney disease (CKD)-associatedAnemia, including non-dialysis-dependent (NDD) patients and dialysis-dependent (DD) patients).FDAThe Prescription Drug User Fee Act (PDUFA) target date has been set for December 20, 2020.
In the United States, roxadustat is approvedFDAThe first oral small-molecule hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor for the treatment of anemia in chronic kidney disease (CKD) has been accepted. The New Drug Application (NDA) for this drug is based on data from a global Phase III program involving more than 8,000 patients.
Chronic kidney disease (CKD) is a progressive disorder characterized by the gradual loss of kidney function, which may ultimately lead to kidney failure or end-stage renal disease (ESRD), necessitating dialysis or kidney transplantation for survival. The global prevalence of CKD among adults is estimated at 10–12%. Anemia is particularly prevalent in patients with CKD, and severe anemia can be life-threatening. CKD-associated anemia increases the risk of hospitalization, cardiovascular complications, and mortality, and often causes severe fatigue.Cognitive Impairmentand a decline in quality of life. There is a significant unmet medical need among patients with anemia associated with chronic kidney disease (CKD), with limited progress made over the past 30 years.
FibroGen stated that it will collaborate withFDAWork closely with partnersAstraZenecacollaboration to bring this novel oral therapy to patients in the United States as soon as possible. This NDA submission triggered a $50 million milestone payment from AstraZeneca to FibroGen.
FibroGen CEO Enrique Conterno stated: “FDA“Acceptance of the new drug application for roxadustat is a critical step toward providing a new treatment option for patients with chronic kidney disease (CKD) and anemia in the United States, as renal anemia is a serious and often life-threatening condition.”
Renal anemia is one of the major complications during the decompensated phase of renal function in chronic kidney disease (CKD). As CKD progresses, the prevalence and severity of CKD-associated anemia gradually increase. Renal anemia is more refractory to correction than conventional anemia, leading to severe fatigue and reduced quality of life in patients. Currently, the standard treatment for renal anemia involves erythropoietin (EPO) replacement therapy using erythropoiesis-stimulating agents (ESAs), such as epoetin alfa, combined with intravenous iron supplementation, administered via subcutaneous injection, to elevate hemoglobin (Hb) levels and improve clinical symptoms in CKD patients.
Roxadustat is the first small-molecule hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) approved globally 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 modulating the role of PH in maintaining the balance between HIF synthesis and degradation, ultimately correcting anemia.
As the first HIF-PHI globally, roxadustat promotes endogenous erythropoietin production, improves iron absorption and utilization, reduces hepcidin levels, and effectively stimulates erythropoiesis without being negatively affected by inflammation on hemoglobin and red blood cell production. Roxadustat has been proven to induce erythropoiesis. In multiple subgroups of patients with chronic kidney disease, roxadustat can maintain erythropoietin levels at or near the normal physiological range, thereby increasing red blood cell count. It is unaffected by inflammatory states and also avoids the need for intravenous iron supplementation.
In December 2018, roxadustat (brand name: Evrenzo) was first approved in China for the treatment of anemia in patients with chronic kidney disease (CKD) on dialysis. In August 2019, the drug received approval in China for a new indication: the treatment of anemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). As a global first-in-class innovative drug, roxadustat was first fully implemented in China for both dialysis-dependent and non-dialysis-dependent CKD patients with anemia, bringing a novel therapeutic breakthrough to the broad population of Chinese patients with chronic kidney disease.
Roxadustat was discovered by FibroGen and is being developed in collaboration with AstraZeneca for the US, Chinese, and other markets, and with Astellas Pharma for Japan and the European Union. In Japan, roxadustat has been approved for the treatment of dialysis-dependent patients, and a supplemental application for the treatment of non-dialysis-dependent patients has been submitted. Astellas Pharma plans to submit a Marketing Authorization Application (MAA) for roxadustat in the first half of 2020. (Bioon.com)