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 antibodie ...
targeting
CC chemokine receptor type 4 (CCR4).
It is given by
injection into a vein
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
.
The most common side effects include rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.
Mogamulizumab was approved for medical use in Japan in 2012. It was approved for medical use in the United States and the European Union in 2018.
It was approved for medical use in Canada in 2022. The US
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) considers it to be a
first-in-class medication
A first-in-class medication is a prototype drug 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 medic ...
.
Medical uses
Mogamulizumab is
indicated
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for the treatment of adults with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy.
History
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) l ...
in the
Fc region
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This region allows antibodies to activate the immune sys ...
.
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 immunity, cell-mediated immune defense whereby an effector cell of the immune system kills a target ...
. 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 Corporation, company headquartered in Thousand Oaks, California. As one of the world's largest independent biotechnology companies, Amgen has a ...
in 2008, for $100 million up front and $420 million in biodollars.[ Amgen ran a Phase I study to explore its use in asthma.]priority review
Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...
for cutaneous T cell lymphoma. Full approval was granted by the FDA in August 2018.vorinostat
Vorinostat (International Nonproprietary Name, rINN), also known as suberoylanilide hydroxamic acid (suberic acid, suberoyl+aniline, anilide+hydroxamic acid abbreviated as SAHA), is a member of a larger class of compounds that inhibit histone de ...
. The FDA granted the application for mogamulizumab priority review, breakthrough therapy
Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...
, and orphan drug
An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...
designations. The FDA granted the approval of Poteligeo to Kyowa Kirin, Inc.
Society and culture
Legal status
The US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approved mogamulizumab in August 2018, for the 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 lesio ...
and Sézary disease.[ ] Mogamulizumab was approved in Japan in 2012, for the treatment of relapsed or refractory CCR4+ adult T-cell leukemia/lymphoma and in 2014, for relapsed or refractory CCR4+ cutaneous T cell lymphoma.[ The latter approval was based on study with 28 participants.
Mogamulizumab was approved for medical use in the European Union in November 2018,]
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
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{{Authority control
Monoclonal antibodies for tumors
Orphan drugs