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Voxelotor

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Voxelotor
Clinical data
Trade namesOxbryta
Other namesGBT440, GBT-440
AHFS/Drugs.comMonograph
MedlinePlusa620011
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • 2-Hydroxy-6-{[2-(1-isopropyl-1H-pyrazol-5-yl)-3-pyridinyl]methoxy}benzaldehyde
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H19N3O3
Molar mass337.379 g·mol−1
3D model (JSmol)
  • CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
  • InChI=1S/C19H19N3O3/c1-13(2)22-16(8-10-21-22)19-14(5-4-9-20-19)12-25-18-7-3-6-17(24)15(18)11-23/h3-11,13,24H,12H2,1-2H3
  • Key:FWCVZAQENIZVMY-UHFFFAOYSA-N

Voxelotor, sold under the brand name Oxbryta, was a medication used for the treatment of sickle cell disease.[1][3][4][5][6] Voxelotor is the first hemoglobin oxygen-affinity modulator.[7] Voxelotor had been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators in sickle cell patients.[8] It initially appeared to have an acceptable safety profile in sickle cell patients and healthy volunteers, without any dose-limiting toxicity noted in clinical trials.[9] It was developed by Global Blood Therapeutics, a subsidiary of Pfizer.[10]

In November 2019, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease for those twelve years of age and older.[11][12] The U.S. Food and Drug Administration (FDA) considered it to be a first-in-class medication.[13] In December 2021, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease for those aged four to eleven years.[14]

In September 2024, Pfizer announced a voluntary withdrawal of voxelotor from all global markets due to concerns regarding the potential for severe safety events, including fatalities.[2][15][16][17]

Side effects

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Common side effects include headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia (fever).[11]

History

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Voxelotor was granted accelerated approval by the US Food and Drug Administration (FDA) in November 2019.[12][11][18] The FDA granted the application for voxelotor fast track designation and orphan drug designation.[11][19]

The approval of voxelotor was based on the results of a clinical trial with 274 participants with sickle cell disease.[11] The FDA granted the approval of Oxbryta to Global Blood Therapeutics.[11][12]

Society and culture

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In December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Oxbryta, intended for the treatment of hemolytic anemia due to sickle cell disease.[20][21] The applicant for this medicinal product is Global Blood Therapeutics Netherlands B.V.[20][21] Voxelotor (Oxbryta) was approved for medical use in the European Union in February 2022.[2][22]

In September 2024, the CHMP recommended suspending the marketing authorization for voxelotor (Oxbryta). The CHMP described this recommendation as a precaution while a review of additional clinical trial data was proceeding.[23] The CHMP review of clinical trial data began in July 2024, following concerns in two ongoing placebo-controlled clinical trials that raised the possibility that the drug's benefit risk ratio was no longer favorable, due to possibly related excess deaths. The CHMP also cited observational studies which found a higher rate of painful vaso-occlusive crises during treatment with voxelotor than the subjects had before starting the medicine.[24]

In September 2024, Pfizer announced a voluntary withdrawal of voxelotor from all global markets due to concerns regarding the potential for severe safety events, including fatalities.[2][15][16][25]

References

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  1. ^ a b "Oxbryta- voxelotor tablet, film coated". DailyMed. 3 December 2019. Retrieved 22 January 2020.
  2. ^ a b c d "Oxbryta EPAR". European Medicines Agency. 14 December 2021. Retrieved 20 April 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ^ "Voxelotor for Sickle Cell Disease". Global Blood Therapeutics. Retrieved 9 December 2018.
  4. ^ "Voxelotor (Previously GBT440)". Sickle Cell Anemia News. Retrieved 13 December 2018.
  5. ^ "ASH 2017: The HbS Polymerization Inhibitor Voxelotor GBT440 Has Demonstrated Positive Initial Results in Adolescents With Sickle Cell Disease". PracticeUpdate. Retrieved 16 December 2018.
  6. ^ Adamson L (22 January 2018). "Voxelotor: A New Option for Young Patients With Sickle Cell Disease?". ASH Clinical News. Retrieved 16 December 2018.
  7. ^ "Voxelotor". PubChem. Retrieved 9 December 2018.
  8. ^ Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, et al. (August 2019). "A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease". The New England Journal of Medicine. 381 (6): 509–519. doi:10.1056/NEJMoa1903212. PMID 31199090.
  9. ^ Hutchaleelaha A, Patel M, Washington C, Siu V, Allen E, Oksenberg D, et al. (June 2019). "Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease". British Journal of Clinical Pharmacology. 85 (6): 1290–1302. doi:10.1111/bcp.13896. PMC 6533444. PMID 30743314.
  10. ^ "Pfizer Completes Acquisition of Global Blood Therapeutics" (Press release). 5 October 2022.
  11. ^ a b c d e f "FDA approves novel treatment to target abnormality in sickle cell disease". U.S. Food and Drug Administration (FDA). 25 November 2019. Archived from the original on 25 November 2019. Retrieved 25 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ a b c "Drug Approval Package: Oxbryta". U.S. Food and Drug Administration (FDA). 23 December 2019. Retrieved 22 January 2020.
  13. ^ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
  14. ^ "FDA approves drug to treat sickle cell disease in patients aged 4 up to 11 years". U.S. Food and Drug Administration (FDA) (Press release). 17 December 2021. Retrieved 17 December 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  15. ^ a b Feuerstein A, Mast J (25 September 2024). "Pfizer pulls sickle cell treatment Oxbryta off global markets". STAT. Retrieved 26 September 2024.
  16. ^ a b "Pfizer withdraws sickle cell disease treatment on risk of complication, death". Reuters. 25 September 2024. Retrieved 26 September 2024.
  17. ^ "FDA is alerting patients and health care professionals about the voluntary withdrawal of Oxbryta from the market due to safety concerns". U.S. Food and Drug Administration. 26 September 2024. Retrieved 15 October 2024.
  18. ^ "Drug Trials Snapshots: Oxbryta". U.S. Food and Drug Administration (FDA). 11 December 2019. Archived from the original on 15 December 2019. Retrieved 15 December 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  19. ^ "Voxelotor Orphan Drug Designation". U.S. Food and Drug Administration (FDA). 25 November 2019. Archived from the original on 26 November 2019. Retrieved 25 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  20. ^ a b "Oxbryta: Pending EC decision". European Medicines Agency. 17 December 2021. Retrieved 18 December 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. ^ a b "New treatment for sickle cell disease". European Medicines Agency (RMA) (Press release). 17 December 2021. Retrieved 18 December 2021.
  22. ^ "Oxbryta Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  23. ^ "EMA recommends suspension of sickle cell disease medicine Oxbryta". European Medicines Agency (EMA) (Press release). 26 September 2024. Retrieved 28 September 2024.
  24. ^ "Oxbryta - referral". European Medicines Agency (EMA). 26 September 2024. Retrieved 28 September 2024.
  25. ^ "Pfizer Voluntarily Withdraws All Lots of Sickle Cell Disease Treatment Oxbryta (voxelotor) From Worldwide Markets". Pfizer. 25 September 2024. Retrieved 28 September 2024.
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