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Last updated: 1 Nov 2012

Masitinib

Summary
Trade name: 
N/A
Class: 
Immunomodulator [[1334]]
Target: 
KIT (a stem cell factor, also called c-KIT) receptor as well as select other tyrosine kinases [[1334]]
Mast cells [[1334]]
Status for MS: 
Phase III [[1378]] [[1381]]
Administration: 
Oral [[1378]]
Commercial: 
Under development by AB Science [[1378]]
Names
Name: 
Masitinib
Trade name: 
N/A
Synonyms: 
4-((4-Methylpiperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)-1,3-thiazol-2-yl)amino)phenyl)benzamide [[465]]
AB 1010 [[465]]
AB-1010 [[465]]
AB1010 [[465]]
Masitinib [[465]]
UNII-M59NC4E26P [[465]]
Systematic name: 
4-((4-Methylpiperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)-1,3-thiazol-2-yl)amino)phenyl)benzamide [[465]]
Physiology
Class: 
Immunomodulator [[1334]]
Target: 
KIT (a stem cell factor, also called c-KIT) receptor as well as select other tyrosine kinases [[1334]]
Mast cells [[1334]]
Properties: 
Toxicity and pharmacokinetics have been studied in dogs [[1379]] [[1380]]
Specificity compared to other tyrosine kinase inhibitors (such as imatinib) may improve safety profile [[1334]]

Mechanisms/Effects

Human: 
Blocks the stem cell factor receptor KIT (also called the c-KIT receptor) in cultured cells [[1334]]
Blocks platelet derived growth factor receptor in cultured cells [[1334]]
Does not target kinases thought to be involved in cardiotoxicity such as ABL, based on experiments in cultured cells [[1334]]
Inhibits human mast cell degranulation, cytokine production, and migration of bone marrow cells in cultured cells [[1334]]
Slowed cognitive decline in Alzheimer disease in a Phase II study, presumably by acting on mast cells in the brain [[1335]]
Likely regulates inflammation indirectly, via mast cells’ release of proinflammatory mediators and control of blood-brain barrier permeability [[1335]]
Improved symptoms of rheumatoid arthritis in a Phase II study [[1336]]
Animal: 
Inhibits tumor growth in vivo in mice [[1334]]
Does not damage chromosomes or affect mitosis in mouse cells [[1334]]
Regulatory and Commercial Status
Status for MS: 
Phase III [[1378]] [[1381]]
Highest status achieved (for any condition): 
Marketing Authorization Application for the treatment of pancreatic cancer has been filed with the European Medicines Agency (16 October 2012) [[3768]]
Marketing Authorization Application for the conditional approval in the treatment of pancreatic cancer has been accepted by the European Medicines Agency (30 October 2012) [[3769]]
Other uses: 
Canine mast cell tumors (registered for veterinary use in US and UK) [[1384]]
Pancreatic cancer (investigational) [[1378]]
Gastrointestinal stromal tumors (investigational) [[1378]]
Multiple myeloma (investigational) [[1378]]
Metastatic solid tumors (investigational) [[1378]]
Mastocytosis (investigational) [[1378]]
Rheumatoid arthritis (investigational) [[1378]]
Asthma (investigational) [[1378]]
Alzheimer disease (investigational) [[1378]]
Administration: 
Oral [[1378]]
Negative effects: 
Abdominal pain [[1335]] [[1337]]
Anemia[ [1337]]
Asthenia [[1337]]
Diarrhea [[1335]] [[1337]]
Edema [[1335]] [[1337]]
Nausea [[1335]] [[1337]]
Neutropenia [[1337]]
Rash [[1335]] [[1337]]
Commercial: 
Under development by AB Science [[1378]]
Key Clinical Trials
Placebo-controlled Trials: 
Trial name: 
Masitinib in Patients with Progressive or Relapse-Free Secondary Multiple Sclerosis [[1382]]
Phase: 
Phase III [[1381]] [[1382]]
Study Design: 
Company-sponsored, prospective, multicenter, randomized, placebo-controlled study examining the safety and efficacy of drug (6 mg/kg/day) judged by changes in multiple sclerosis functional composite score (primary outcome) [[1382]]
Disease Stage: 
PPMS or SPMS [[1381]] [[1382]]
Enrollment/Number of Patients: 
Estimated enrollment 450 patients [[1381]] [[1382]]
Duration: 
96 weeks [[1381]] [[1382]]
Status/Outcome: 
Recruiting patients; results expected after December, 2014 [[1382]]
Trial name: 
Masitinib in Patients with Primary Progressive Multiple Sclerosis (PPMS) or Relapse-Free Secondary Multiple Sclerosis (SPMS) (Published June 2012) [[1383]] [[2122]]
Phase: 
Phase II [[1383]] [[2122]]
Study Design: 
Company-sponsored, randomized, placebo-controlled trial testing the safety and efficacy of two doses of drug (3 mg/kg/day and 6 mg/kg/day) as measured by changes in multiple sclerosis functional composite (MSFC) score (primary outcome) [[1383]] [[2122]]
Disease Stage: 
PPMS or SPMS [[1383]] [[2122]]
Enrollment/Number of Patients: 
35 patients [[1383]] [[2122]]
Duration: 
12 months [[1383]] [[2122]]
Status/Outcome: 
Out of 35 patients, 27 received drug and 8 received placebo. Of those, 7/17 assessable patients – 41% -- reported clinical response to treatment, but the response was not statistically significant: the change in MSFC score was +103% +/- 189 (drug) versus -60% +/- 190 (placebo) at month 12. The drug was also associated with a higher incidence of more severe adverse events [[1383]] [[2122]]
Head-to-Head Trials: 
Other Trials: 
References
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 4 Jan 2012 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

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