Chemistry:Roxadustat

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Short description: Anti-anemia medication
Roxadustat
Roxadustat.svg
Clinical data
Trade namesEvrenzo
Other namesFG-4592, ASP1517, AZD9941
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • EU: Rx-only [1]
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC19H16N2O5
Molar mass352.346 g·mol−1
3D model (JSmol)

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.

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

Due to roxadustat's potential applications in athletic doping, such as raising haemoglobin levels and stimulating the production of red blood cells,[11] it has been incorporated into screens for performance-enhancing drugs, as it has already been detected being used illicitly by athletes.[12][13][14] In October 2022, it was announced that Romanian former world No. 1 tennis player Simona Halep had tested positive for roxadustat at the 2022 US Open.[15] In September 2023, she was banned from the game for four years by the International Tennis Integrity Agency (ITIA) for two anti-doping violations: taking roxadustat, and anomalies in her athlete biological passport.[11]

FDA rejection

On July 15, 2021, the FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against roxadustat's use in patients with anemia in chronic kidney disease, both for those that are non-dialysis-dependent and those that are on dialysis.[16] Significant safety concerns were raised that the panelists believed could not be addressed without further study.[17] Notably, prior to FDA committee's vote, 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.[18]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Evrenzo EPAR". 23 June 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/evrenzo.  Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. ↑ "Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD". Clinical Journal of the American Society of Nephrology 11 (6): 982–991. June 2016. doi:10.2215/CJN.06890615. PMID 27094610. 
  3. ↑ "A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat". Advances in Therapy 34 (4): 848–853. April 2017. doi:10.1007/s12325-017-0508-9. PMID 28290095. 
  4. ↑ "Roxadustat: First Global Approval". Drugs 79 (5): 563–572. April 2019. doi:10.1007/s40265-019-01077-1. PMID 30805897. 
  5. ↑ "Roxadustat: First Global Approval". Drugs 79 (5): 563–572. April 2019. doi:10.1007/s40265-019-01077-1. PMID 30805897. 
  6. ↑ "Astellas Receives Approval of Evrenzo (roxadustat) in Japan for the Treatment of Anemia of Chronic Kidney Disease in Adult Patients Not on Dialysis". Astellas. 2020-11-27. https://newsroom.astellas.us/2020-11-27-Astellas-Receives-Approval-of-EVRENZO-R-roxadustat-in-Japan-for-the-Treatment-of-Anemia-of-Chronic-Kidney-Disease-in-Adult-Patients-Not-on-Dialysis. 
  7. ↑ "Evrenzo Product information". https://ec.europa.eu/health/documents/community-register/html/h1574.htm. 
  8. ↑ "The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model". Scientific Reports 9 (1): 6035. April 2019. doi:10.1038/s41598-019-41924-5. PMID 30988335. Bibcode: 2019NatSR...9.6035Z. 
  9. ↑ "Roxadustat: another drug that causes pulmonary hypertension? Report of first human case". Polish Archives of Internal Medicine 129 (5): 344–345. May 2019. doi:10.20452/pamw.4445. PMID 30758318. 
  10. ↑ "Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis". The New England Journal of Medicine 381 (11): 1001–1010. September 2019. doi:10.1056/NEJMoa1813599. PMID 31340089. 
  11. ↑ 11.0 11.1 "Simona Halep given four-year ban from tennis for anti-doping violations". The Guardian. 12 September 2023. https://www.theguardian.com/sport/2023/sep/12/simona-halep-banned-four-years-tennis-anti-doping-violations. 
  12. ↑ "Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis". Drug Testing and Analysis 4 (11): 830–845. November 2012. doi:10.1002/dta.390. PMID 22362605. 
  13. ↑ "Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case". Journal of Pharmaceutical and Biomedical Analysis 121: 181–187. March 2016. doi:10.1016/j.jpba.2016.01.029. PMID 26808067. 
  14. ↑ "lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls". Drug Testing and Analysis 9 (11–12): 1768–1778. November 2017. doi:10.1002/dta.2202. PMID 28378453. 
  15. ↑ "Simona Halep vows to 'fight for the truth' after positive doping test". The Guardian. 21 October 2022. https://www.theguardian.com/sport/2022/oct/21/simona-halep-suspended-doping-test-wimbledon-champion-tennis. 
  16. ↑ "FibroGen Announces Outcome of FDA Advisory Committee Review of Roxadustat for Treatment of Anemia of Chronic Kidney Disease | FibroGen, Inc.". https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-outcome-fda-advisory-committee-review. 
  17. ↑ "AstraZeneca, FibroGen hit another roxadustat setback as FDA panel calls for more safety data". 15 July 2021. https://www.fiercepharma.com/pharma/astrazeneca-fibrogen-hit-another-roxadustat-setback-as-fda-panel-calls-for-more-safety-data. 
  18. ↑ "FibroGen admits to messing with roxadustat safety data, upending hopes for the AZ-partnered anemia drug" (in en). 2021-04-07. https://www.fiercepharma.com/pharma/fibrogen-admits-to-messing-safety-data-for-anemia-drug-roxadustat-as-analysts-dramatically. 

Further reading

External links



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