Masitinib Explained

Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumours in animals, specifically dogs.[1] [2] Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. Masitinib has been studied for several human conditions including melanoma, multiple myeloma, gastrointestinal cancer, pancreatic cancer, Alzheimer disease, multiple sclerosis, rheumatoid arthritis, mastocytosis, amyotrophic lateral sclerosis and COVID-19.[3] [4] [5]

Mechanism of action

Masitinib is a tyrosine kinase inhibitor which inhibits tyrosine kinases, enzymes responsible for the activation of many proteins by signal transduction cascades. Specifically, masitinib targets the receptor tyrosine kinase c-Kit which is found to be overexpressed or mutated in several types of cancer.[6] Masitinib is also additional targets, it also inhibits the platelet derived growth factor receptor (PDGFR), lymphocyte-specific protein tyrosine kinase (Lck), focal adhesion kinase (FAK) and fibroblast growth factor receptor 3 (FGFR3) as well as CSF1R.[7] [8]

Masitinib has been shown to block the replication of SARS-CoV-2 by inhibiting its main protease, 3CLpro. Masitinib showed >200-fold reduction in viral titers in the lungs and nose of mice infected with SARS-CoV-2.

Society and culture

Legal status

Masitinib was under investigation for the treatment of systemic mastocytosis (Masipro) but approval was denied in the EU in 2017 due to concerns "about the reliability of the study results" and major changes to the study design.[9] [10] [11]

European approval of masitinib for treatment of amyotrophic lateral sclerosis (Alsitek) was also refused in 2018.[12] [13]

In June 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended the refusal of a marketing authorization for Masitinib AB Science, a medicine intended for the treatment of amyotrophic lateral sclerosis, a rare disease of the nervous system leading to loss of muscle function and paralysis.[14] [15]

Notes and References

  1. Hahn KA, Ogilvie G, Rusk T, Devauchelle P, Leblanc A, Legendre A, Powers B, Leventhal PS, Kinet JP, Palmerini F, Dubreuil P, Moussy A, Hermine O . 6 . Masitinib is safe and effective for the treatment of canine mast cell tumors . Journal of Veterinary Internal Medicine . 22 . 6 . 1301–1309 . 2008 . 18823406 . 10.1111/j.1939-1676.2008.0190.x . free .
  2. Information about Masivet at the European pharmacy agency website
  3. Drayman N, DeMarco JK, Jones KA, Azizi SA, Froggatt HM, Tan K, Maltseva NI, Chen S, Nicolaescu V, Dvorkin S, Furlong K, Kathayat RS, Firpo MR, Mastrodomenico V, Bruce EA, Schmidt MM, Jedrzejczak R, Muñoz-Alía MÁ, Schuster B, Nair V, Han KY, O'Brien A, Tomatsidou A, Meyer B, Vignuzzi M, Missiakas D, Botten JW, Brooke CB, Lee H, Baker SC, Mounce BC, Heaton NS, Severson WE, Palmer KE, Dickinson BC, Joachimiak A, Randall G, Tay S . 6 . Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2 . Science . 373 . 6557 . 931–936 . August 2021 . 34285133 . 8809056 . 10.1126/science.abg5827 . free . 2021Sci...373..931D .
  4. Web site: Orphan designation EU/3/16/1722 for masitinib mesilate for the treatment of amyotrophic lateral sclerosis. . European Medicines Agency . 17 September 2018 . 29 November 2016 . 17 October 2017 . https://web.archive.org/web/20171017203401/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Forphans%2F2016%2F10%2Fhuman_orphan_001821.jsp . dead .
  5. Folch J, Petrov D, Ettcheto M, Pedrós I, Abad S, Beas-Zarate C, Lazarowski A, Marin M, Olloquequi J, Auladell C, Camins A . 6 . Masitinib for the treatment of mild to moderate Alzheimer's disease . Expert Review of Neurotherapeutics . 15 . 6 . 587–596 . June 2015 . 25961655 . 10.1586/14737175.2015.1045419 . 39839943 .
  6. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W, Voisset E, Arock M, Auclair C, Leventhal PS, Mansfield CD, Moussy A, Hermine O . 6 . Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT . PLOS ONE . 4 . 9 . e7258 . September 2009 . 19789626 . 2746281 . 10.1371/journal.pone.0007258 . 2009PLoSO...4.7258D . free .
  7. Gil da Costa RM . C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic . Veterinary Journal . 205 . 1 . 5–10 . July 2015 . 26021891 . 10.1016/j.tvjl.2015.05.002 . free . 10216/103345 .
  8. Trias E, Ibarburu S, Barreto-Núñez R, Babdor J, Maciel TT, Guillo M, Gros L, Dubreuil P, Díaz-Amarilla P, Cassina P, Martínez-Palma L, Moura IC, Beckman JS, Hermine O, Barbeito L . 6 . Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis . Journal of Neuroinflammation . 13 . 1 . 177 . July 2016 . 27400786 . 4940876 . 10.1186/s12974-016-0620-9 . free .
  9. Web site: European Medicines Agency . Masipro EPAR . 18 May 2017 . 12 July 2024 . 30 May 2023 . https://web.archive.org/web/20230530185605/https://www.ema.europa.eu/en/medicines/human/EPAR/masipro . live .
  10. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/004159/WC500228053.pdf Refusal of the marketing authorisation for Masipro (masitinib).
  11. Web site: Masipro (masitinib) . Union Register of refused medicinal products for human use . Public Health - European Commission . 12 July 2024 . 11 June 2018 . https://web.archive.org/web/20180611201606/http://ec.europa.eu/health/documents/community-register/html/ho26274.htm . live .
  12. Web site: Alsitek EPAR . European Medicines Agency . 18 April 2018 . 12 July 2024 . 10 August 2023 . https://web.archive.org/web/20230810002336/https://www.ema.europa.eu/en/medicines/human/EPAR/alsitek . live .
  13. Web site: Alsitek (masitinib) . Union Register of refused medicinal products for human use . Public Health - European Commission.
  14. Web site: Masitinib AB Science EPAR . European Medicines Agency (EMA) . 27 June 2024 . 12 July 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  15. Web site: Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024 . European Medicines Agency . 28 June 2024 . 12 July 2024 . 12 July 2024 . https://web.archive.org/web/20240712152232/https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2024 . live .

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