Chemistry:Mogamulizumab
| 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 |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6520H10072N1736O2020S42 |
| Molar mass | 146444.95 g·mol−1 |
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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]
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
- ↑ 1.0 1.1 "Poteligeo". 15 February 2021. https://www.tga.gov.au/apm-summary/poteligeo.
- ↑ 2.0 2.1 "AusPAR: Mogamulizumab". 10 May 2021. https://www.tga.gov.au/auspar/auspar-mogamulizumab.
- ↑ "Poteligeo Product information". 25 April 2012. https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=101691.
- ↑ "Summary Basis of Decision - Poteligeo". 23 October 2014. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00611&lang=en.
- ↑ 5.0 5.1 5.2 "Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering". BioDrugs 31 (3): 151–166. June 2017. doi:10.1007/s40259-017-0223-8. PMID 28466278. https://eprints.soton.ac.uk/410615/1/Resubmission_Yu_Manuscript_and_table.pdf.
- ↑ 6.0 6.1 "FDA approves treatment for two rare types of non-Hodgkin lymphoma" (Press release).
- ↑ "Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease". Cancer Treatment Reviews 60: 120–129. November 2017. doi:10.1016/j.ctrv.2017.09.002. PMID 28946015.
- ↑ 8.0 8.1 "Clinical Application of Anti-CCR4 Monoclonal Antibody". Oncology 89 (Suppl 1): 16–21. 2015. doi:10.1159/000431059. PMID 26550987.
- ↑ "Available Agents: Mogamulizumab" (in en). NCI Formulary. https://nciformulary.cancer.gov/available_agents/Mogamulizumab.htm.
- ↑ 10.0 10.1 Carroll, John (25 August 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints. https://endpts.com/after-a-long-clinical-odyssey-the-fda-tapped-this-phiii-anti-ccr4-as-a-breakthrough-lymphoma-drug/.
- ↑ 11.0 11.1 "Recent progress in the development of antagonists to the chemokine receptors CCR3 and CCR4". Expert Opinion on Drug Discovery 9 (5): 467–83. May 2014. doi:10.1517/17460441.2014.897324. PMID 24641500.
- ↑ Adamson, Laurie (22 January 2018). "Mogamulizumab Receives Priority Review for CTCL - ASH Clinical News". ASH Clinical News. https://www.ashclinicalnews.org/news/mogamulizumab-receives-priority-review-ctcl/.
- ↑ (PDF) New Drug Therapy Approvals 2018 (Report). January 2019. https://www.fda.gov/media/120357/download. Retrieved 16 September 2020.
- ↑ "Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy". The New England Journal of Medicine 378 (6): 529–538. February 2018. doi:10.1056/NEJMoa1704827. PMID 29414279.
External links
- "Mogamulizumab". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/mogamulizumab.
- "Mogamulizumab-kpkc". 30 August 2018. https://www.cancer.gov/about-cancer/treatment/drugs/mogamulizumabkpkc.
- "Mogamulizumab-kpkc". NCI Drug Dictionary. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/mogamulizumab.
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