Mogamulizumab
Mogamulizumab, sold under the brand name Poteligeo, is a humanized, afucosylated monoclonal antibody targeting CC chemokine receptor 4 (CCR4).[4] The U.S. Food and Drug Administration (FDA) approved it in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease.[5] 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).[4] The latter approval was based on study with 28 subjects.[6]
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Humanized (from mouse) |
Target | CCR4 |
Clinical data | |
Pronunciation | moe gam" ue liz' ue mab |
Trade names | Poteligeo |
Other names | mogamulizumab-kpkc |
AHFS/Drugs.com | Monograph |
MedlinePlus | a618064 |
License data | |
Pregnancy category | |
Routes of administration | Intravenous |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
|
UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6520H10072N1736O2020S42 |
Molar mass | 146444.95 g·mol−1 |
(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.[4][7] This is thought to enhance its antibody-dependent cell-mediated cytotoxicity.[8] It was first tested in humans in 2007.[7]
Kyowa licensed rights for use outside of cancer to Amgen in 2008, for $100 million up front and $420 million in biodollars.[9] Amgen ran a Phase I study to explore its use in asthma.[10] Amgen terminated the agreement in 2014.[9]
As of 2014, there were reports that mogamulizimab can cause serious skin rashes and some cases of Stevens–Johnson syndrome.[10]
In 2017, the US FDA granted it a priority review for CTCL.[11] Full approval was granted in August 2018.[5] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[12]
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.[13]
References
- "Poteligeo". Therapeutic Goods Administration (TGA). 15 February 2021. Retrieved 8 September 2021.
- "AusPAR: Mogamulizumab". Therapeutic Goods Administration (TGA). 10 May 2021. Retrieved 8 September 2021.
- "Poteligeo Product information". Health Canada. Retrieved 30 September 2022.
- 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.
- "FDA approves treatment for two rare types of non-Hodgkin lymphoma" (Press release).
- 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.
- Ueda R (2015). "Clinical Application of Anti-CCR4 Monoclonal Antibody". Oncology. 89 Suppl 1: 16–21. doi:10.1159/000431059. PMID 26550987. S2CID 24091636.
- "Available Agents: Mogamulizumab". NCI Formulary. Retrieved 11 May 2018.
- Carroll J (August 25, 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints.
- 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.
- Adamson L (22 January 2018). "Mogamulizumab Receives Priority Review for CTCL - ASH Clinical News". ASH Clinical News.
- New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
- 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.
External links
- "Mogamulizumab". Drug Information Portal. U.S. National Library of Medicine.
- "Mogamulizumab-kpkc". National Cancer Institute. 30 August 2018.
- "Mogamulizumab-kpkc". NCI Drug Dictionary. National Cancer Institute.