Roxadustat (Evrenzo) NDA Review by FDA Extended by Three Months; First-in-Class HIF-PH Inhibitor for CKD Anemia Already Launched in China

December 20, 2020 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) and its partner FibroGen recently jointly announced that the U.S. Food and Drug Administration (FDA) has requested both parties to further clarify the clinical data analysis to complete the renalAnemiaReview of the New Drug Application (NDA) for Evrenzo (Chinese brand name: Airuizhuo; generic name: roxadustat), a new drug indicated for the treatment of anemia associated with chronic kidney disease (CKD), including patients who are non-dialysis-dependent (NDD) and dialysis-dependent (DD).

Notably, roxadustat is the first orally administered small-molecule hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor accepted by the FDA for the treatment of anemia in chronic kidney disease (CKD). AstraZeneca and FibroGen have committed to collaborating with the FDA and agreed to submit additional clarifying analyses as soon as possible to facilitate the completion of labeling discussions. The New Drug Application (NDA) remains under regulatory review.FDAThe Prescription Drug User Fee Act (PDUFA) goal date has been extended by three months, from December 20, 2020, to March 20, 2021.

Roxadustat was discovered by FibroGen and is being developed in collaboration with AstraZeneca in the United States, China, and other markets, and with Astellas Pharma in Japan and the European Union. In December 2018, roxadustat (generic name: roxadustat; brand name: Evrenzo) became the first drug to be 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 has pioneered comprehensive application 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.

In addition, roxadustat has also been approved in Japan for the treatment of anemia in adult patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) chronic kidney disease (CKD). In Europe, the marketing authorization application (MAA) for roxadustat for the treatment of NDD and DD CKD anemia in adult patients was submitted by Astellas Pharma and accepted by the European Medicines Agency (EMA) in May 2020.

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 common 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.

Renal anemia is one of the major complications during the decompensated stage 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 alfaepoetin, combined with intravenous iron supplementation. Administered via subcutaneous injection, this regimen aims to elevate hemoglobin (Hb) levels in CKD patients and alleviate clinical symptoms.

Molecular Structure of Roxadustat (Image Source: Wikimedia)

As the world’s first hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), roxadustat promotes endogenous erythropoietin production, improves iron absorption and utilization, reduces hepcidin levels, and effectively stimulates erythropoiesis without being adversely affected by inflammation on hemoglobin and red blood cell production. Roxadustat has been confirmed to induce erythropoiesis. In multiple subpopulations of patients with chronic kidney disease, roxadustat maintains erythropoietin levels at or near the normal physiological range, thereby increasing red blood cell counts. Its efficacy is unaffected by inflammatory status, and it can also avoid the need for intravenous iron supplementation. (Bioon.com)

Original Source: Update on US Regulatory Review of Roxadustat in Anaemia of Chronic Kidney Disease