Background

Masitinib is an orally available inhibitor of the protein tyrosine kinase c-kit that is expressed on cancer cells. It also inhibits PDGF and FGF receptors. Masitinib interferes with the survival, migration, and activity of mast cells, and in this role has attracted attention for the treatment of neuroinflammatory and neurodegenerative disorders.

Findings

From 2006 to 2009, AB Science conducted a Phase 2 trial comparing 3 and 6 mg/kg/day of Masitinib or placebo, taken twice daily for six months as an add-on therapy to cholinesterase inhibitor and/or memantine treatment. Conducted at 12 centers in France, this trial enrolled 34 patients with mild to moderate Alzheimer's disease and used change in cognition as measured by the ADAS-Cog as primary outcome. Masitinib was reported to have reduced cognitive decline in this study, with a claimed effect size of 6.8 and 7.6 at three and six months, respectively. Side effects including gastrointestinal disorders, edema, and rash occurred about twice as often with masitinib than placebo. Nineteen of 34 participants in the masitinab group withdrew before the study completed, compared with two of the eight placebo participants. Seven of the 19 withdrawals were reported as due to treatment-related adverse effects. The drug's tolerance was called acceptable in this report (Piette et al., 2011).

In 2012, a Phase 3 trial began. Conducted in Madrid, it is enrolling 396 patients with mild to moderate Alzheimer's disease into a six-month study comparing 3 or 4.5 mg/kg/day or placebo as an add-on to cholinesterase and memantine treatment. Cognition as measured by ADAS-cog and global function as measured by the ADCS-ADL are coprimary outcome measures. The trial is expected to run through 2015.

In addition, masitinib is being evaluated in Spain for amyotrophic lateral sclerosis as an add-on therapy to riluzole. This trial started in January 2013 as a Phase 2 with 45 patients but was expanded into a Phase 3 study with 210 patients (see EU Clinical Trials Register; see news release). This study will run through 2015.

Masitinib is in late-stage development for pancreatic cancer. It is also being developed for multiple sclerosis, mood disorders, asthma, chronic obstructive pulmonary disease, mastocytosis, and rheumatoid arthritis. Masitinib is in clinical trials for breast, colorectal, gastric, head and neck, liver, lung, and oesophageal cancer, as well as glioblastoma, metastatic melanoma, multiple myeloma, and T cell lymphoma. The drug is available in veterinary medicine under the names Masivet or Kinavet.

For all trials of masitinib in Alzheimer's, see clinicaltrials.gov.

Clinical Trial Timeline