Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 5/2019

01-04-2019 | Erythropoietin | AdisInsight Report

Roxadustat: First Global Approval

Author: Sohita Dhillon

Published in: Drugs | Issue 5/2019

Login to get access

Abstract

Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. Inhibition of these enzymes reduces HIF breakdown and promotes HIF activity, leading to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability and increases haemoglobin levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism. Roxadustat is approved in China and is under regulatory review in Japan for the treatment of anaemia in patients with dialysis-dependent CKD. Studies are underway to investigate long-term cardiovascular outcomes with roxadustat versus placebo (for non-dialysis-dependent CKD) or standard of care (for dialysis-dependent CKD). This article summarizes the milestones in the development of roxadustat leading to this first approval.
Literature
1.
Becker K, Saad M. A new approach to the management of anemia in CKD patients: a review on roxadustat. Adv Ther. 2017;34(4):848–53.CrossRefPubMed
2.
Locatelli F, Fishbane S, Block GA, et al. Targeting hypoxia-inducible factors for the treatment of anemia in chronic kidney disease patients. Am J Nephrol. 2017;45(3):187–99.CrossRefPubMed
3.
Gupta N, Wish JB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: a potential new treatment for anemia in patients with CKD. Am J Kidney Dis. 2017;69(6):815–26.CrossRefPubMed
4.
Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis. 2018;71(3):423–35.CrossRefPubMed
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Besarab A, Provenzano R, Hertel J, et al. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015;30(10):1665–73.CrossRefPubMedPubMedCentral
16.
17.
Chen N, Qian J, Chen J, et al. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. Nephrol Dial Transplant. 2017;32(8):1373–86.CrossRefPubMedPubMedCentral
18.
Provenzano R, Besarab A, Sun CH, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment of anemia in patients with CKD. Clin J Am Soc Nephrol. 2016;11(6):982–91.CrossRefPubMedPubMedCentral
19.
Yu KH, Chou J, Klaus S, et al. Comparable doses of FG-4592 have similar PK/PD in healthy Caucasian and Japanese subjects (abstract no. MP204). Nephrol Dial Transplant. 2013;28(Suppl 1):i362.
20.
Chen X, Zheng X, Jiang J, et al. FG4592, a novel inhibitor of the prolyl hydroxylase of hypoxia-inducible factor (HIF-PH) elicited linear-exponential dose-response profile on plasma erythropoietin (EPO) levels (abstract no. P413). Haematologica. 2013;98(Suppl 1):175–6.
21.
Shibata T, Nomura Y, Takada A, et al. Evaluation of food and spherical carbon adsorbent effects on the pharmacokinetics of roxadustat in healthy nonelderly adult male Japanese subjects. Clin Pharmacol Drug Dev. 2018. https://​doi.​org/​10.​1002/​cpdd.​597.
22.
Groenendaal-van de Meent D, Adel MD, Noukens J, et al. Effect of moderate hepatic impairment on the pharmacokinetics and pharmacodynamics of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. Clin Drug Investig. 2016;36(9):743–51.
23.
24.
Shibata T, Nomura Y, Takada A, et al. Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non-elderly healthy adult male subjects. J Clin Pharm Ther. 2018;43(5):633–9.CrossRefPubMed
25.
Groenendaal-van de Meent D, den Adel M, Rijnders S, et al. The hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat (FG-4592) and warfarin in healthy volunteers: a pharmacokinetic and pharmacodynamic drug-drug interaction study. Clin Ther. 2016;38(4):918–28.
26.
27.
Chen N, Hao C-M, Liu B-C, et al. A phase 3, randomized, open-label, active-controlled study of efficacy and safety of roxadustat for treatment of anemia in subjects with CKD on dialysis (abstract no. TH-PO1152). J Am Soc Nephrol. 2018;29(Suppl):B5.
28.
Akizawa T, Iwasaki M, Yamaguchi Y, et al. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) conversion study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan (abstract no. TH-PO1151). J Am Soc Nephrol. 2018;29(Suppl):B4–B5.
29.
Akizawa T, Otsuka T, Reusch M, et al. Phase 3, multicenter, open-label study of intermittent oral roxadustat in peritoneal dialysis CKD patients with anemia (abstract no. SA-OR075). J Am Soc Nephrol. 2018;29(Suppl):99.
30.
31.
Provenzano R, Besarab A, Wright S, et al. Roxadustat (FG-4592) versus epoetin alfa for anemia in patients receiving maintenance hemodialysis: a phase 2, randomized, 6- to 19-week, open-label, active-comparator, dose-ranging, safety and exploratory efficacy study. Am J Kidney Dis. 2016;67(6):912–24.CrossRefPubMed
32.
Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients. J Am Soc Nephrol. 2016;27(4):1225–33.CrossRefPubMed
33.
34.
Chen N, Hao C-M, Peng X, et al. A phase 3, randomized, double-blind, placebo-controlled study of efficacy and safety of roxadustat (FG-4592) for treatment of anemia in subjects with CKD not on dialysis (abstract no. TH-PO1153). J Am Soc Nephrol. 2018;29(Suppl.):B5.
Metadata
Title
Roxadustat: First Global Approval
Author
Sohita Dhillon
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Drugs / Issue 5/2019
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-019-01077-1

Other articles of this Issue 5/2019

Drugs 5/2019 Go to the issue

Correction

Correction to: Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia

Correction

Correction to: Fremanezumab: First Global Approval

AdisInsight Report

Tagraxofusp: First Global Approval

Correction

Correction to: Tapentadol Prolonged Release: A Review in Pain Management

Leading Article

Phenylketonuria: Current Treatments and Future Developments

Therapy in Practice

Management of Post-transplant Hyperparathyroidism and Bone Disease