Voxelotor

Last updated

Voxelotor
Voxelotor skeletal.svg
Clinical data
Trade names Oxbryta
Other namesGBT440, GBT-440
AHFS/Drugs.com Monograph
MedlinePlus a620011
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
Formula C19H19N3O3
Molar mass 337.379 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]

Contents

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

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

History

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

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]

Related Research Articles

Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

<span class="mw-page-title-main">Momelotinib</span> Medication

Momelotinib, sold under the brand name Ojjaara among others, is an anticancer medication used for the treatment of myelofibrosis. It is a Janus kinase inhibitor and it is taken by mouth.

<span class="mw-page-title-main">Difelikefalin</span> Chemical compound

Difelikefalin, sold under the brand name Korsuva, is an opioid peptide used for the treatment of moderate to severe itch. It acts as a peripherally-restricted, highly selective agonist of the κ-opioid receptor (KOR).

Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.

<span class="mw-page-title-main">Migalastat</span> Chemical compound

Migalastat, sold under the brand name Galafold, is a medication for the treatment of Fabry disease, a rare genetic disorder. It was developed by Amicus Therapeutics. The US Food and Drug Administration (FDA) granted it orphan drug status in 2004, and the European Commission followed in 2006. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) granted the drug a marketing approval under the name Galafold in May 2016.

Crizanlizumab, sold under the brand name Adakveo among others, is a monoclonal antibody medication that binds to P-selectin. It is a medication used to reduce the frequency of vaso-occlusive crisis in people aged 16 years and older who have sickle cell anemia. It is given by injection into a vein.

<span class="mw-page-title-main">Lorlatinib</span> Kinase inhibitor for treatment of non-small-cell lung cancer

Lorlatinib, sold under the brand name Lorbrena in the United States, Canada, and Japan, and Lorviqua in the European Union, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is an orally administered inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), two enzymes that play a role in the development of cancer. It was developed by Pfizer.

<span class="mw-page-title-main">Erdafitinib</span> Chemical compound

Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.

<span class="mw-page-title-main">Tepotinib</span> Chemical compound

Tepotinib, sold under the brand name Tepmetko, is an anti-cancer medication used for the treatment of adults with non-small cell lung cancer (NSCLC).

Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). It is given by intravenous infusion. Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro.

Tagraxofusp, sold under the brand name Elzonris, is an anti-cancer medication for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.

<span class="mw-page-title-main">Zanubrutinib</span> Chemical compound

Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL). Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

<span class="mw-page-title-main">Adagrasib</span> Medication

Adagrasib, sold under the brand name Krazati, is an anticancer medication used to treat non-small cell lung cancer. Adagrasib is an inhibitor of G12C mutated KRAS GTPase. It is taken by mouth. It is being developed by Mirati Therapeutics.

Spesolimab, sold under the brand name Spevigo, is a monoclonal antibody used for the treatment of generalized pustular psoriasis (GPP). It is an interleukin-36 receptor (IL-36R) antagonist. It is given via injection into a vein.

<span class="mw-page-title-main">Iptacopan</span> Chemical compound

Iptacopan, sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It is a complement factor B inhibitor that was developed by Novartis. It is taken by mouth.

Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy used for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. It was developed by Vertex Pharmaceuticals and CRISPR Therapeutics.

References

  1. 1 2 "Oxbryta- voxelotor tablet, film coated". DailyMed. 3 December 2019. Retrieved 22 January 2020.
  2. 1 2 3 4 "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. 1 2 3 4 5 6 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. 1 2 3 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. 1 2 Feuerstein A, Mast J (25 September 2024). "Pfizer pulls sickle cell treatment Oxbryta off global markets". STAT. Retrieved 26 September 2024.
  16. 1 2 "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.PD-icon.svg 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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  20. 1 2 "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. 1 2 "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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.