Mogamulizumab, sold under the brand name Poteligeo, is a humanized, afucosylated

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

targeting CC chemokine receptor 4 (CCR4). The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) approved it in August 2018 for treatment of relapsed or refractory

mycosis fungoides Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions ...

and Sézary disease. 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). The latter approval was based on study with 28 subjects. 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 is a Japanese pharmaceutical and biotechnology company under the Kirin Holdings, and is among the 40 largest in the world by revenue. The company is headquartered in Chiyoda-ku, Tokyo and is a member of the Nikkei 225 stock index. History On ...

. 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 Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...

in the Fc region. This is thought to enhance its

antibody-dependent cell-mediated cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose ...

. It was first tested in humans in 2007. Kyowa licensed rights for use outside of cancer to

Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was established in T ...

in 2008, for $100 million up front and $420 million in biodollars. Amgen ran a Phase I study to explore its use in asthma. Amgen terminated the agreement in 2014. As of 2014, there were reports that mogamulizimab can cause serious skin rashes and some cases of

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

. In 2017, the US FDA granted it a priority review for CTCL. Full approval was granted in August 2018. The U.S.

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

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.

References

External links

* * * Monoclonal antibodies Orphan drugs {{antineoplastic-drug-stub