Roxadustat

Roxadustat, sold under the brand name Evrenzo, is an anti-anemia medication. Roxadustat is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of erythropoietin and stimulates production of hemoglobin and red blood cells. It was investigated in clinical trials for the treatment of anemia caused by chronic kidney disease (CKD).^[2][3] It is taken by mouth.^[1] The drug was developed by FibroGen, in partnership with AstraZeneca.

Roxadustat

Clinical data
Trade names	Evrenzo
Other names	FG-4592, ASP1517, AZD9941
Routes of administration	By mouth
ATC code	B03XA05 (WHO)
Legal status
Legal status	EU: Rx-only[1] In general: ℞ (Prescription only)
Identifiers
IUPAC name 2-[(4-Hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid
CAS Number	808118-40-3
PubChem CID	11256664
DrugBank	DB04847
ChemSpider	9431690
UNII	X3O30D9YMX
KEGG	D10593
CompTox Dashboard (EPA)	DTXSID60230644
ECHA InfoCard	100.245.356
Chemical and physical data
Formula	C19H16N2O5
Molar mass	352.346 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NC(=C(C2=C1C=C(C=C2)OC3=CC=CC=C3)O)C(=O)NCC(=O)O
InChI InChI=1S/C19H16N2O5/c1-11-15-9-13(26-12-5-3-2-4-6-12)7-8-14(15)18(24)17(21-11)19(25)20-10-16(22)23/h2-9,24H,10H2,1H3,(H,20,25)(H,22,23) Key:YOZBGTLTNGAVFU-UHFFFAOYSA-N

The most common side effects include hypertension (high blood pressure), vascular access thrombosis (formation of blood clots in the blood vessels associated with dialysis), diarrhea, peripheral edema (swelling especially of the ankles and feet), hyperkalemia (high blood potassium levels) and nausea (feeling sick).^[1]

Roxadustat received its first global approval in China on 17 December 2018,^[4] for the treatment of anemia caused by CKD in patients who are dialysis-dependent.^[5] It was approved in Japan in 2019, for the treatment of anemia caused by CKD in patients on dialysis, and in 2020 for patients not on dialysis.^[6] Roxadustat was approved for medical use in the European Union in August 2021.^[1][7]

Medical uses

Roxadustat is indicated for treatment of adults with symptomatic anemia associated with chronic kidney disease (CKD).^[1]

Adverse effects

Roxadustat is reported to increase VEGF, a signal protein that can activate tumor growth^[8] and also is considered to cause pulmonary hypertension.^[9] In phase 3 trial conducted at 29 sites in China, roxadustat treatment was found to cause hyperkalemia, i.e., increase in serum potassium, and metabolic acidosis in patients.^[10]

Society and culture

Legal status

In July 2021, the Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted against the use of roxadustat in people with anemia in chronic kidney disease, both for those that are non-dialysis-dependent and those that are on dialysis.^[11] Significant safety concerns were raised that the panelists believed could not be addressed without further study.^[12] Notably, prior to the vote of the FDA committee, FibroGen and AstraZeneca announced that the company had changed parameters used to analyze cardiovascular safety data, which made the drug appear safer than it is.^[13]

Usage as a doping product

Due to the potential applications of roxadustat in athletic doping, such as raising haemoglobin levels and stimulating the production of red blood cells,^[14] it has been incorporated into screens for performance-enhancing drugs, as it has already been detected being used illicitly by athletes.^[15][16][17] In March 2024, following a lengthly process, former world No. 1 tennis player Simona Halep received a nine month ban for unintentional use of roxadustat that was sourced to a contaminated supplement that she had ingested.^[14][18][19]