Masitinib significantly slows the progression of disability on the EDSS score
in patients with primary progressive multiple sclerosis (PPMS)
and secondarily non-active multiple sclerosis (nSPMS)
AB Science SA (Euronext - FR0010557264 - AB) announces today that the phase 2B / 3 study (AB07002) evaluating oral masitinib in the treatment of primary progressive multiple sclerosis (PPMS) and sclerosis secondarily progressive non-active plaque therapy (nSPMS) reached its main objective (p = 0.0256) at a dose of 4.5 mg / kg / day. This treatment effect was conserved digitally in the PPMS and nSPMS subpopulations.
The study enrolled 301 patients in the treatment arm at 4.5 mg / kg / day (200 patients treated with masitinib and 101 treated with placebo). The predefined main evaluation criterion was the variation of the EDSS score compared to its initial value, on the basis of all the measurements made between week 12 and week 96. The results on the main evaluation criterion are confirmed by l predefined and significantly significant sensitivity analysis based on the EDSS ordinal model. In addition, masitinib significantly slowed the progression of the disease, measured by the duration to reach an EDSS score of 7.0 (which corresponds to a handicap severe enough for the patient to travel with a wheelchair).
The efficacy analysis was performed in the modified intention-to-treat (mITT) population, which includes all randomized patients who received at least one dose of the study treatment (masitinib / placebo).
The proportion of patients with at least one adverse event was 95.0% for masitinib (4.5 mg / kg / day) compared to 87.1% for placebo. The tolerance of the product was in accordance with the known risk profile of the product.
The study also enrolled 310 patients in the treatment arm at a dose of 6 mg / kg / day (dose adjustment with a start at 4.5 mg / kg / day, 203 patients treated with masitinib and 107 patients treated with a placebo). No significant improvement was seen with masitinib at this higher dose compared to placebo.
Professor Patrick Vermersch, director of the Department of Neurology at the University of Lille in France and coordinating investigator of the AB07002 study, said: "Patients with primary progressive multiple sclerosis (PPMS) and secondarily progressive multiple sclerosis non-active (nSPMS) represent half of the population with multiple sclerosis. Although many treatment options based on targeting B cells and T cells of the acquired immune system are available for patients with relapsing-remitting forms of multiple sclerosis, these treatments have failed or have been inconclusive. PPMS and nSPMS. Therefore, there is still a very important medical need in these two indications. Since masitinib does not target the acquired immune system, the results of this study constitute a major scientific advance since it is the first time that this new strategy of targeting the innate immune system, via mast cells and microglia, has significantly slowed the progression of clinical disability in progressive forms of multiple sclerosis. These results are extremely encouraging and could bring new hope for patients with progressive forms of multiple sclerosis. "
Professor Olivier Hermine (Chairman of the Scientific Committee of AB Science and member of the Académie des Sciences) said: "This positive result in progressive forms of multiple sclerosis constitutes a new key fact which further validates the mechanism of action of masitinib in neurodegenerative diseases . This is indeed the second piece of evidence from the masitinib development program. The first evidence was the positive phase 2B / 3 study of masitinib in amyotrophic lateral sclerosis (ALS) . The second proof is this new positive phase 2B / 3 study in progressive forms of multiple sclerosis, a disease which shares characteristics similar to neurodegenerative diseases. These two studies now clearly demonstrate that targeting the innate immune system via macrophages / microglia and mast cells, which corresponds to the mechanism of action of masitinib, appears to be one of the relevant strategies in the treatment of degenerative disorders. This is a real innovation that justifies AB Science’s long-term efforts to develop masitinib in ALS, progressive forms of multiple sclerosis and Alzheimer’s disease. "
A new patent has been filed based on the results of study AB07002.
The company will approach health authorities to discuss the next steps in the development of masitinib in the treatment of progressive forms of multiple sclerosis.
AB Science will present the detailed results of the study at an upcoming scientific conference. These results will also be detailed at a web conference on masitinib in progressive forms of multiple sclerosis that AB Science will hold in the coming years with key opinion leaders.
: Stys PK and Tsutsui S. F1000Res. 2019 Dec 13; 8. pii: F1000 Faculty Rev-2100.
: Mora JS et al. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Jul 7: 1-10.
Phase 3 study in primary progressive multiple sclerosis and non-active secondarily progressive multiple sclerosis
The Phase 2B / 3 study (AB07002) was a prospective, multicenter, randomized (2: 1), double-blind, placebo-controlled study that aimed to evaluate masitinib as a treatment for progressive forms of multiple sclerosis , at a dose of 4.5 mg / kg / day and at a dose of 6 mg / kg / day (dose adjustment starting at 4.5 mg / kg / day). Patients with primary progressive multiple sclerosis or non-active secondarily progressive multiple sclerosis were treated for 96 weeks. They were between 18 and 75 years of age and their Expanded Disability Status Scale (EDSS) score was between 2.0 and 6.0 at the time of entry into the study, regardless of how soon symptoms first started.
The predefined main evaluation criterion was the overall variation of the EDSS score from its initial value, based on repeated measurements (GEE model, between week 12 and week 96). The predefined sensitivity analysis was based on the ordinal EDSS model (GEE model, between week 12 and week 96).
Masitinib is a new oral tyrosine kinase inhibitor that targets mast cells and macrophages, essential cells of immunity, by inhibiting a limited number of kinases. Due to its unique mode of action, masitinib can be developed in a large number of pathologies, in oncology, in inflammatory diseases, and certain diseases of the central nervous system. In oncology, by its immunotherapy activity, masitinib can have an effect on survival, alone or in combination with chemotherapy. By its activity on the mast cell and microglial cells and therefore by its inhibitory effect on the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with certain inflammatory pathologies and of the central nervous system.
About AB Science
Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development and marketing of inhibitors of protein kinases (IPK), a class of targeted proteins whose action is decisive in cell signaling. Our programs target only pathologies with a high medical need, often fatal with a low survival rate, rare, or resistant to a first line of treatment.
AB Science has developed its own portfolio of molecules and AB Science's flagship molecule, masitinib, has already been registered in veterinary medicine and is developed in humans in oncology, in neurodegenerative diseases and in inflammatory diseases. The Company is headquartered in Paris and is listed on Euronext Paris (Ticker: AB).
More information about the Company on the website: www.ab-science.com
Source (in French): https://www.globenewswire.com/news-rele ... aques.html
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http://www.ab-science.com/years/2020/19 ... orms-of-ms
▪ Masitinib significantly delays disability progression measured by average change in EDSS either in
absolute value or ordinal change
▪ Probability of having either more disease improvements or fewer disease progressions is significantly
increased by 39% with masitinib
▪ Time to first progression is significantly delayed by 42% and time to confirmed progression is delayed
▪ The safety profile appears acceptable in the targeted indication.
▪ Masitinib compares favorably vis-à-vis ocrevus, siponimod, and biotin.