Mogamulizumab

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Mogamulizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target CCR4
Clinical data
Pronunciationmoe gam" ue liz' ue mab
Trade names Poteligeo
Other namesmogamulizumab-kpkc
AHFS/Drugs.com Monograph
MedlinePlus a618064
License data
Pregnancy
category
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
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 type 4 (CCR4). [5] [7] It is given by injection into a vein. [5] [6]

Contents

The most common side effects include rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. [8]

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. [5] [6] It was approved for medical use in Canada in 2022. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [9]

Medical uses

Mogamulizumab is indicated for the treatment of adults with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. [5] [6] [8]

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. 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. [7] [10] This is thought to enhance its antibody-dependent cell-mediated cytotoxicity. [11] It was first tested in humans in 2007. [10]

Kyowa licensed rights for use outside of cancer to Amgen in 2008, for $100 million up front and $420 million in biodollars. [12] Amgen ran a Phase I study to explore its use in asthma. [13] Amgen terminated the agreement in 2014. [12]

In 2017, the US FDA granted the application for mogamulizumab a priority review for cutaneous T cell lymphoma. [14] Full approval was granted by the FDA in August 2018. [8] The FDA approval was based on a clinical trial of 372 participants with relapsed mycosis fungoides or Sézary syndrome who received either mogamulizumab or a type of chemotherapy called vorinostat. The FDA granted the application for mogamulizumab priority review, breakthrough therapy, and orphan drug designations. The FDA granted the approval of Poteligeo to Kyowa Kirin, Inc.

Society and culture

The US Food and Drug Administration (FDA) approved mogamulizumab in August 2018, [15] for the treatment of relapsed or refractory mycosis fungoides and Sézary disease. [8] 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. [7] The latter approval was based on study with 28 participants. [16]

Mogamulizumab was approved for medical use in the European Union in November 2018, [6] and in Canada in June 2022.

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. [17]

Related Research Articles

<span class="mw-page-title-main">Mycosis fungoides</span> Most common form of cutaneous T-cell lymphoma

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 itchy skin.

<span class="mw-page-title-main">Cutaneous T-cell lymphoma</span> Medical condition

Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas, CTCL is caused by a mutation of T cells. The cancerous T cells in the body initially migrate to the skin, causing various lesions to appear. These lesions change shape as the disease progresses, typically beginning as what appears to be a rash which can be very itchy and eventually forming plaques and tumors before spreading to other parts of the body.

<span class="mw-page-title-main">Sézary disease</span> Medical condition

Sézary disease, or Sézary syndrome, is a type of cutaneous T-cell lymphoma that was first described by Albert Sézary. The affected T cells, known as Sézary's cells or Lutzner cells, have pathological quantities of mucopolysaccharides. Sézary disease is sometimes considered a late stage of mycosis fungoides with lymphadenopathy.

Tositumomab is a murine monoclonal antibody which targets the CD20 antigen produced in mammalian cell. It was combined with iodine-131 to produce a radiopharmaceutical for unsealed source radiotherapy, Iodine-131 Tositumomab, for the treatment of non-Hodgkins lymphoma. It is classified as a IgG2a lambda antibody.

<span class="mw-page-title-main">Inotuzumab ozogamicin</span> Chemical compound

Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It is administered by intravenous infusion.

Blinatumomab, sold under the brand name Blincyto, and known informally as blina, is a biopharmaceutical medication used as a second-line treatment for Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells. In December 2014, it was approved by the US Food and Drug Administration under the accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval. Blinatumomab is given via intravenous infusion.

<span class="mw-page-title-main">Bi-specific T-cell engager</span> Class of artificial monoclonal antibodies

Bi-specific T-cell engagers (BiTEs) are a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells' cytotoxic activity, against cancer cells. BiTE is a registered trademark of Micromet AG.

MorphoSys AG is a German biopharmaceutical company founded in 1992. The company is headquartered near Munich, Germany, and has a wholly owned subsidiary, MorphoSys US Inc., in Boston, Massachusetts, in the US. The company has various antibody, protein and peptide technologies that it uses to discover and develop both proprietary and partnered drug candidates. The company has more than 100 drugs in its wider pipeline that are being investigated for a variety of diseases. While many of these are being developed in partnership with pharma and biotech companies, MorphoSys also has a proprietary pipeline with a focus on cancer and autoimmune diseases.

<span class="mw-page-title-main">Lutzner cells</span>

Lutzner cells were discovered by Marvin A. Lutzner, Lucien-Marie Pautrier, and Albert Sézary. These cells are described as the smaller forms of Sézary cells, or Sézary-Lutzner cells, and the two variants are recognised as being morphologically different. Aggregates of these cells in mycosis fungoides are known as a Pautrier's microabscesses. They are a form of T-lymphocytes that has been mutated This atypical form of T-lymphocytes contains T-cell receptors on the surface and is found in both the dermis and epidermis layers of the skin. Since Lutzner cells are a mutated form of T-lymphocytes, they develop in bone marrow and are transported to the thymus is order to mature. The production and maturation stages occur before the cell has developed a mutation. Lutzner cells can form cutaneous T-cell lymphoma, which is a form of skin cancer.

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.

Seagen Inc. is an American biotechnology company focused on developing and commercializing innovative, empowered monoclonal antibody-based therapies for the treatment of cancer. The company, headquartered in Bothell, Washington, is the industry leader in antibody-drug conjugates or ADCs, a technology designed to harness the targeting ability of monoclonal antibodies to deliver cell-killing agents directly to cancer cells. Antibody-drug conjugates are intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy, while potentially enhancing antitumor activity.

Polatuzumab vedotin, sold under the brand name Polivy, is a CD79b-directed antibody-drug conjugate medication used for the treatment of diffuse large B-cell lymphoma (cancer). It was developed by the Genentech subsidiary of Roche.

<span class="mw-page-title-main">Duvelisib</span> PI3K inhibitor

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<span class="mw-page-title-main">Loncastuximab tesirine</span> Medication

Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.

<span class="mw-page-title-main">Selinexor</span> Anti-cancer drug

Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.

Tafasitamab, sold under the brand name Monjuvi, is a medication used in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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References

  1. 1 2 "Poteligeo". Therapeutic Goods Administration (TGA). 15 February 2021. Archived from the original on 9 September 2021. Retrieved 8 September 2021.
  2. 1 2 "AusPAR: Mogamulizumab". Therapeutic Goods Administration (TGA). 10 May 2021. Archived from the original on 9 September 2021. Retrieved 8 September 2021.
  3. ↑ "Poteligeo Product information". Health Canada . 25 April 2012. Archived from the original on 1 October 2022. Retrieved 30 September 2022.
  4. ↑ "Summary Basis of Decision - Poteligeo". Health Canada . 23 October 2014. Archived from the original on 28 November 2022. Retrieved 28 November 2022.
  5. 1 2 3 4 5 "Poteligeo- mogamulizumab-kpkc injection". DailyMed. 27 April 2023. Retrieved 15 May 2024.
  6. 1 2 3 4 5 "Poteligeo EPAR". European Medicines Agency (EMA). 14 October 2016. Archived from the original on 5 July 2021. Retrieved 15 May 2024.
  7. 1 2 3 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. Archived (PDF) from the original on 26 August 2021. Retrieved 15 May 2024.
  8. 1 2 3 4 "FDA approves treatment for two rare types of non-Hodgkin lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 8 August 2018. Archived from the original on 15 July 2021. Retrieved 15 May 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Archived from the original on 17 September 2020. Retrieved 16 September 2020.
  10. 1 2 Ueda R (2015). "Clinical Application of Anti-CCR4 Monoclonal Antibody". Oncology. 89 (Suppl 1): 16–21. doi:10.1159/000431059. PMID   26550987. S2CID   24091636.
  11. ↑ "Available Agents: Mogamulizumab". NCI Formulary. Archived from the original on 11 May 2018. Retrieved 11 May 2018.
  12. 1 2 Carroll J (25 August 2017). "After a long clinical odyssey, the FDA tapped this PhIII anti-CCR4 as a 'breakthrough' lymphoma drug". Endpoints. Archived from the original on 31 October 2021. Retrieved 11 May 2018.
  13. ↑ 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.
  14. ↑ Adamson L (22 January 2018). "Mogamulizumab Receives Priority Review for CTCL - ASH Clinical News". ASH Clinical News. Archived from the original on 10 May 2018. Retrieved 10 May 2018.
  15. ↑ "Drug Approval Package: Poteligeo (mogamulizumab-kpkc)". U.S. Food and Drug Administration (FDA). 7 September 2018. Retrieved 15 May 2024.
  16. ↑ 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.
  17. ↑ 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.
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