Mogamulizumab

Mogamulizumab, sold under the brand name Poteligeo, is a humanized, afucosylated monoclonal antibody targeting CC chemokine receptor 4 (CCR4).[5] The U.S. Food and Drug Administration (FDA) approved it in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease.[6] It was approved in Japan in 2012, for the treatment of relapsed or refractory CCR4+ adult T-cell leukemia/lymphoma (ATCLL) and in 2014, for relapsed or refractory CCR4+ cutaneous T cell lymphoma (CTCL).[5] The latter approval was based on study with 28 subjects.[7]

Mogamulizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetCCR4
Clinical data
Pronunciationmoe gam" ue liz' ue mab
Trade namesPoteligeo
Other namesmogamulizumab-kpkc
AHFS/Drugs.comMonograph
MedlinePlusa618064
License data
Pregnancy
category
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6520H10072N1736O2020S42
Molar mass146444.95 g·mol−1
 ☒NcheckY (what is this?)  (verify)

The precursor to mogamulizumab was a mouse anti-human CCR4 IgG1 mAb (KM2160), that was made in 1996 in a collaboration between Kouji Matsushima of University of Tokyo and Kyowa Hakko Kirin. Kyowa humanized it, and expressed the humanized gene in a CHO cell line in which FUT8 had been knocked out, which produced antibodies with no fucose in the Fc region.[5][8] This is thought to enhance its antibody-dependent cell-mediated cytotoxicity.[9] It was first tested in humans in 2007.[8]

Kyowa licensed rights for use outside of cancer to Amgen in 2008, for $100 million up front and $420 million in biodollars.[10] Amgen ran a Phase I study to explore its use in asthma.[11] Amgen terminated the agreement in 2014.[10]

As of 2014, there were reports that mogamulizimab can cause serious skin rashes and some cases of Stevens–Johnson syndrome.[11]

In 2017, the US FDA granted it a priority review for CTCL.[12] Full approval was granted in August 2018.[6] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[13]

Research

Mogamulizumab is being explored as a treatment for HTLV-1–Associated Myelopathy. An early Phase 1-2a study showed decreased in proviral loads, as well as inflammatory markers in the CSF. 79% of the patients showed reduction in spasticity and 32% showed decrease in motor disability.[14]

References
  1. "Poteligeo". Therapeutic Goods Administration (TGA). 15 February 2021. Retrieved 8 September 2021.
  2. "AusPAR: Mogamulizumab". Therapeutic Goods Administration (TGA). 10 May 2021. Retrieved 8 September 2021.
  3. "Poteligeo Product information". Health Canada. 25 April 2012. Retrieved 30 September 2022.
  4. "Summary Basis of Decision - Poteligeo". Health Canada. 23 October 2014. Retrieved 28 November 2022.
  5. Yu X, Marshall MJ, Cragg MS, Crispin M (June 2017). "Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering" (PDF). BioDrugs. 31 (3): 151–166. doi:10.1007/s40259-017-0223-8. PMID 28466278. S2CID 3722081.
  6. "FDA approves treatment for two rare types of non-Hodgkin lymphoma" (Press release).
  7. Broccoli A, Argnani L, Zinzani PL (November 2017). "Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease". Cancer Treatment Reviews. 60: 120–129. doi:10.1016/j.ctrv.2017.09.002. PMID 28946015.
  8. Ueda R (2015). "Clinical Application of Anti-CCR4 Monoclonal Antibody". Oncology. 89 (Suppl 1): 16–21. doi:10.1159/000431059. PMID 26550987. S2CID 24091636.
  9. "Available Agents: Mogamulizumab". NCI Formulary. Retrieved 11 May 2018.
  10. Carroll J (25 August 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints.
  11. Pease JE, Horuk R (May 2014). "Recent progress in the development of antagonists to the chemokine receptors CCR3 and CCR4". Expert Opinion on Drug Discovery. 9 (5): 467–83. doi:10.1517/17460441.2014.897324. PMID 24641500. S2CID 32596704.
  12. Adamson L (22 January 2018). "Mogamulizumab Receives Priority Review for CTCL - ASH Clinical News". ASH Clinical News.
  13. New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
  14. Sato T, Coler-Reilly AL, Yagishita N, Araya N, Inoue E, Furuta R, et al. (February 2018). "Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy". The New England Journal of Medicine. 378 (6): 529–538. doi:10.1056/NEJMoa1704827. PMID 29414279.


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