Daprodustat Explained

Width:200
Tradename:Duvroq, Jesduvroq
Dailymedid:Daprodustat
Routes Of Administration:By mouth
Class:Hypoxia-inducible factor prolyl hydroxylase inhibitor
Atc Prefix:B03
Atc Suffix:XA07
Legal Us:Rx-only
Legal Us Comment:[1]
Legal Status:Rx-only
Cas Number:960539-70-2
Pubchem:91617630
Drugbank:DB11682
Chemspiderid:33427356
Unii:JVR38ZM64B
Kegg:D10874
Chebi:229223
Chembl:3544988
Synonyms:GSK1278863
Iupac Name:2-[(1,3-dicyclohexyl-2,4,6-trioxo-1,3-diazinane-5-carbonyl)amino]acetic acid
C:19
H:27
N:3
O:6
Smiles:C3CCCCC3n(c(=O)c1C(=O)NCC(=O)O)c(=O)n(c1O)C2CCCCC2
Stdinchi:1S/C19H27N3O6/c23-14(24)11-20-16(25)15-17(26)21(12-7-3-1-4-8-12)19(28)22(18(15)27)13-9-5-2-6-10-13/h12-13,26H,1-11H2,(H,20,25)(H,23,24)
Stdinchikey:NVTKJBXOBFRPLQ-UHFFFAOYSA-N

Daprodustat, sold under the brand name Duvroq among others, is a medication that is used for the treatment of anemia due to chronic kidney disease. It is a hypoxia-inducible factor prolyl hydroxylase inhibitor. It is taken by mouth.

The most common side effects include high blood pressure, thrombotic vascular events, abdominal pain, dizziness, and allergic reactions.

Daprodustat was approved for medical use in Japan in June 2020,[2] [3] and in the United States in February 2023.[4] [5] [6] making it the first oral treatment for anemia caused by chronic kidney disease for adults in the US. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]

Medical uses

Daprodustat is indicated for the treatment of anemia due to chronic kidney disease.

Daprodustat increases erythropoietin levels.

Adverse effects

The FDA label for daprodustat has a boxed warning for an increased risk of thrombotic vascular (blood clotting) events including death, heart attack, stroke, and blood clots in the lung, legs, or dialysis access site.[8]

The most common side effects include high blood pressure, thrombotic vascular events, abdominal pain, dizziness, and allergic reactions.

History

The efficacy and safety of daprodustat were evaluated in 2,964 adults with anemia due to chronic kidney disease on dialysis and receiving an erythropoiesis-stimulating agent at the time of study entry in a randomized, sponsor-blind, active-controlled, global, multicenter, event-driven clinical trial (ASCEND-D; NCT02879305). Participants were stratified by dialysis type and were required to be on dialysis for at least four months prior to the first dose of daprodustat. Participants on hemodialysis were randomized 1:1 to receive oral daprodustat (N=1,316) or intravenous epoetin alfa (N=1,308) while participants on peritoneal dialysis were randomized 1:1 to receive oral daprodustat (N=171) or subcutaneous darbepoetin alfa (N=169). In this study, adults received either oral daprodustat or injected recombinant human erythropoietin (a standard of care treatment for people with anemia due to chronic kidney disease). Daprodustat raised and maintained the hemoglobin (the protein in red blood cells that carries oxygen and is a common measure of anemia) within the target range of 10 to 11 g/dL, similar to that of the treatment. The trial was conducted at 431 sites in 35 countries.

The FDA granted the approval of Jesduvroq to GlaxoSmithKline LLC.

Society and culture

Due to its potential applications in athletic doping, it has also been incorporated into screens for performance-enhancing drugs.[9]

Research

Daprodustat is in phase III clinical trials for the treatment of anemia caused by chronic kidney disease.[10] [11] [12]

Notes and References

  1. Web site: Jesduvroq- daprodustat tablet, film coated . DailyMed . 1 February 2023 . 11 February 2023 . 11 February 2023 . https://web.archive.org/web/20230211050842/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d82aa06e-5a33-4844-99b7-4701313455a4 . live .
  2. Dhillon S . Daprodustat: First Approval . Drugs . 80 . 14 . 1491–1497 . September 2020 . 32880805 . 7471535 . 10.1007/s40265-020-01384-y .
  3. GSK receives first regulatory approval for Duvroq (daprodustat) in Japan for patients with anaemia due to chronic kidney disease . 29 June 2020 . GSK . 29 March 2021 . 4 February 2023 . https://web.archive.org/web/20230204025837/https://www.gsk.com/en-gb/media/press-releases/gsk-receives-first-regulatory-approval-for-duvroq-daprodustat-in-japan-for-patients-with-anaemia-due-to-chronic-kidney-disease/ . live .
  4. FDA Approves First Oral Treatment for Anemia Caused by Chronic Kidney Disease for Adults on Dialysis . U.S. Food and Drug Administration (FDA) . 1 February 2023 . 3 February 2023 . 4 February 2023 . https://web.archive.org/web/20230204025623/https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-anemia-caused-chronic-kidney-disease-adults-dialysis . live .
  5. Harris E . 15 February 2023 . FDA Approves First Oral Treatment for Kidney Disease–Induced Anemia . JAMA . 329 . 9 . 704 . 10.1001/jama.2023.1556 . 36790833 .
  6. Jesduvroq (daprodustat) approved by US FDA for anemia of chronic kidney disease in adults on dialysis . GSK US . 1 February 2023 . 24 February 2024 . 4 February 2023 . https://web.archive.org/web/20230204025813/https://us.gsk.com/en-us/media/press-releases/jesduvroq-daprodustat-approved-by-us-fda-for-anemia-of-chronic-kidney-disease-in-adults-on-dialysis/ . live .
  7. New Drug Therapy Approvals 2023 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 9 January 2024 . https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download . 10 January 2024 . live .
  8. Web site: Drug Trials Snapshots: Jesduvroq . U.S. Food and Drug Administration (FDA) . 1 February 2023 . 24 February 2024 . 24 February 2024 . https://web.archive.org/web/20240224214047/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-jesduvroq . live .
  9. Thevis M, Milosovich S, Licea-Perez H, Knecht D, Cavalier T, Schänzer W . Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls . Drug Testing and Analysis . 8 . 8 . 858–63 . August 2016 . 26361079 . 10.1002/dta.1870 .
  10. Schmid H, Jelkmann W . Investigational therapies for renal disease-induced anemia . Expert Opinion on Investigational Drugs . 25 . 8 . 901–16 . August 2016 . 27122198 . 10.1080/13543784.2016.1182981 . 32493057 .
  11. Ariazi JL, Duffy KJ, Adams DF, Fitch DM, Luo L, Pappalardi M, Biju M, DiFilippo EH, Shaw T, Wiggall K, Erickson-Miller C . Discovery and Preclinical Characterization of GSK1278863 (Daprodustat), a Small Molecule Hypoxia Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia . The Journal of Pharmacology and Experimental Therapeutics . 363 . 3 . 336–347 . December 2017 . 28928122 . 10.1124/jpet.117.242503 . free .
  12. Singh AK, Carroll K, McMurray JJ, Solomon S, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Więcek A, Blackorby A, Cizman B, Cobitz AR, Davies R, DiMino TL, Kler L, Meadowcroft AM, Taft L, Perkovic V . Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis . The New England Journal of Medicine . 385 . 25 . 2313–2324 . December 2021 . 34739196 . 10.1056/NEJMoa2113380 . 243761990 . free .

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