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    You are here : Home » MS Research News » Drugs » Masitinib


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    Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study

    MasitinibTreatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network.

    Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS).

    Methods: Multicenter, randomized, placebo-controlled, proof-of-concept trial.

    Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC).

    Clinical response was defined as an increase in MSFC score relative to baseline of >100%.

    Results: Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea.

    The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% +/- 189 versus -60% +/- 190 at month-12, respectively.

    This positive albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/17 (41%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group.

    The Expanded Disability Status Scale remained stable for both treatment groups.

    Conclusion: These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation.

    Author: Patrick VermerschRabah BenrabahNicolas SchmidtHélène ZéphirPierre ClavelouCyrille VongsouthiPatrice DubreuilAlain MoussyOlivier Hermine
    Credits/Source: BMC Neurology 2012, 12:36

    Source: 7thSpace Interactive © 2012 7thSpace Interactive (13/06/12)

    First patient recruited in phase 3 study of masitinib in progressive MS

    MasitinibAB Science SA, a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), announced today recruitment of the first patient in the phase 3 study of masitinib in primary progressive multiple sclerosis or relapse free secondary progressive multiple sclerosis.

    This is an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Its objective is to compare the efficacy and safety of masitinib at 6 mg/kg/day with placebo in the treatment of patients with primary progressive multiple sclerosis or relapse free secondary progressive multiple sclerosis. This study will enroll approximately 450 patients, across 60 centers around the world, randomized with a ratio of 2:1 between the masitinib and placebo groups. The primary response evaluation will be the proportion of patients to achieve an improvement of at least 100% in their symptoms, as measured by the Multiple Sclerosis Functional Composite (MSFC) score, after 96 weeks of treatment.

    Professor Patrick Vermersch (CHRU Lille - Hopital Roger Salengro, France), the principal investigator of this study declared: "Masitinib is a selective inhibitor of specific kinases that play a major role in the activation of mast cells, which are cells involved in the immune response, in the recruitment of lymphocytes to the brain, and also in inflammatory processes associated with multiple sclerosis and many of its resulting symptoms. Masitinib therefore represents an oral treatment different from those drugs already on the market for this indication, with a unique mechanism of action in blocking mast cells. In an experimental model of multiple sclerosis (mice immunized with myelin), masitinib demonstrated an ability to delay the onset of symptoms of multiple sclerosis. A phase 2 study of 30 patients in the two subpopulations of progressive multiple sclerosis, which represent approximately 60% of patients and for which there is no satisfactory treatment, has tested masitinib against placebo. The results showed that for the primary endpoint of MSFC (which measures symptoms of patients on three aspects:movement of the lower limbs)(which measures symptoms of patients on three aspects:movement of the upper limbs)(which measures symptoms of patients on three aspects:and cognitive tests) 30% of patients treated with masitinib were responders against 0% under placebo. Responses were seen in the third month and were more-or-less sustained over the study's 18-month duration. Masitinib therefore represents a promising new therapeutic approach in this disease, which justifies the initiation of this Phase 3 study."

    Professor Olivier Hermine, President of the scientific committee of AB Science commented: "Masitinib differs from those treatments currently available or under development in multiple sclerosis. It has a weak immunosuppressive activity, although by inducing a reduction in the number of lymphocytes infiltrating the brain it helps prevent injuries. Masitinib's characteristic selectivity against mast cells also means that it is not associated to date with major toxicities; for example, cardiac toxicity as seen with mitoxantrone, a drug sometimes used in severe progressive multiple sclerosis, or opportunistic infections as seen with Tysabri or Gilenya, which are associated with an increased risk of infection."

    This phase 3 study is fully financed.

    About masitinib

    Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells, important cells for immunity, as well as a limited number of kinases that play key roles in various cancers. Owing to its novel mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases and in certain diseases of the central nervous system. Through its activity of inhibiting certain kinases that are essential in some oncogenic processes, masitinib may have an effect on tumor regression, alone or in combination with chemotherapy. Through its activity on the mast cell and certain kinases essential to the activation of the inflammatory cells and fibrosing tissue remodeling, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases.

    About AB Science

    AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a new class of targeted molecules whose action is to modify signaling pathways within cells. Through these PKIs, the Company targets diseases with high unmet medical needs (cancer, inflammatory diseases and central nervous system diseases), in both human and veterinary medicines. AB Science has developed its own portfolio of molecules including masitinib, which has already been registered in veterinary medicine in Europe and in the USA, and is pursuing nine phase-3 studies in human medicine, including seven studies on-going in pancreatic cancer, GIST, in metastatic melanoma expressing JM mutation of c-Kit, in mastocytosis, severe persistent asthma, rheumatoid arthritis, and in progressive forms of multiple sclerosis.

    Source: AB Science SA (07/09/11)

    © Multiple Sclerosis Resource Centre (MSRC)

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