Mogamulizumab

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]

Mogamulizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetCCR4
Clinical data
Trade namesPoteligeo
Routes of
administration		Intravenous
ATC code
Identifiers
CAS Number
ChemSpider
  • none
KEGG
Chemical and physical data
FormulaC6520H10072N1736O2020S42
Molar mass146.44 kg/mol g·mol−1
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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.[3]

Currently, 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.[10]

References
  1. "Mogamulizumab - Kyowa Hakko Kirin". AdisInsight. Retrieved 11 May 2018.
  2. 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. "Press Announcements - FDA approves treatment for two rare types of non-Hodgkin lymphoma".
  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. 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. Carroll, John (August 25, 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints.
  8. 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. Sato, Tomoo; Coler-Reilly, Ariella L.G.; Yagishita, Naoko; Araya, Natsumi; Inoue, Eisuke; Furuta, Rie; Watanabe, Toshiki; Uchimaru, Kaoru; Matsuoka, Masao; Matsumoto, Naoki; Hasegawa, Yasuhiro; Yamano, Yoshihisa (8 February 2018). "Mogamulizumab (Anti-CCR4) in HTLV-1–Associated Myelopathy". New England Journal of Medicine. 378 (6): 529–538. doi:10.1056/NEJMoa1704827.


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