Mogamulizumab

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Mogamulizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target CCR4
Clinical data
Trade names Poteligeo
Routes of
administration
Intravenous
ATC code
Identifiers
CAS Number
ChemSpider
  • none
KEGG
Chemical and physical data
Formula C6520H10072N1736O2020S42
Molar mass 146.44 kg/mol
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Mogamulizumab (trade name Poteligeo)[1] is a humanized, afucosylated monoclonal antibody targeting CC chemokine receptor 4 (CCR4).[2] The US FDA approved it in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease.[3] 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).[2] The latter approval was based on study with 28 subjects.[4]

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.[2][5] This is thought to enhance its antibody-dependent cell-mediated cytotoxicity.[6] It was first tested in humans in 2007.[5]

Kyowa licensed rights for use outside of cancer to Amgen in 2008 for $100 million up front and $420 million in biodollars.[7] Amgen ran a Phase I study to explore its use in asthma.[8] Amgen terminated the agreement in 2014.[7]

As of 2014 there were reports that mogamulizimab can cause serious skin rashes and some cases of Steven-Johnson syndrome.[8]

Late in 2017 the US FDA granted it a priority review for CTCL.[9] Full approval was granted in August 2018.[10]

References[edit]

  1. ^ "Mogamulizumab - Kyowa Hakko Kirin". AdisInsight. Retrieved 11 May 2018. 
  2. ^ a b c Yu, X; Marshall, MJE; Cragg, MS; Crispin, M (June 2017). "Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering". BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 31 (3): 151–166. doi:10.1007/s40259-017-0223-8. PMID 28466278. 
  3. ^ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616176.htm
  4. ^ 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. 
  5. ^ a b Ueda, R (2015). "Clinical Application of Anti-CCR4 Monoclonal Antibody". Oncology. 89 Suppl 1: 16–21. doi:10.1159/000431059. PMID 26550987. 
  6. ^ "Available Agents: Mogamulizumab". NCI Formulary. Retrieved 11 May 2018. 
  7. ^ a b Carroll, John (August 25, 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints. 
  8. ^ a b 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. 
  9. ^ Adamson, Laurie (22 January 2018). "Mogamulizumab Receives Priority Review for CTCL - ASH Clinical News". ASH Clinical News. 
  10. ^ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616176.htm