PRESS RELEASE
AB SCIENCE PROVIDES AN UPDATE ON THE DEVELOPMENT OF MASITINIB IN PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS FOLLOWING THE ECTRIMS 2024 CONFERENCE
Paris, September 23, 2024, 5:45 p.m. CET
AB Science SA (Euronext – FR0010557264 – AB) today provides an update on the development of masitinib in progressive forms of multiple sclerosis (MS), following the 2024 conference of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
The development of masitinib in progressive forms of multiple sclerosis is based on the MAXIMS study (AB20009), a randomized, double-blind phase 3 study of masitinib at a dose of 4.5 mg/kg/day in patients with primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (nSPMS). The study includes patients with an Expanded Disability Status Scale (EDSS) score between 3.0 and 6.0, disease progression within the last 2 years and an absence of T1-enhancing brain lesions after gadolinium injection. The main objective of the study is to evaluate the effect of masitinib on the time to confirmed progression of disability.
The recent results of tolebrutinib in non-active secondary progressive multiple sclerosis (nSPMS), presented at the ECTRIMS 2024 conference, reinforce the scientific hypothesis that targeting microglia in nSPMS is a relevant approach. Tolebrutinib belongs to a class of drugs that target microglia via an enzyme target called BTK (Bruton Tyrosine Kinase).
Masitinib also targets microglia but via a different enzyme target called M-CSFR1 (Macrophage Colony Stimulating Factor Receptor-1) and has generated positive results in phase 2B/3 (AB07002) [1]which are consistent with the results of tolebrutinib.
- Progression of confirmed EDSS at 3 months was reduced by 37% with masitinib in study AB07002 and by 23% with tolebrutinib in the Hercules study (although the reduction in study AB07002 did not reached the conventional p-value of 5% to the extent that the study did not have the necessary power to detect a statistically significant effect on this criterion, having 300 patients in the masitinib arms at 4.5 mg/kg/day or placebo versus 1,100 patients in the Hercules trial).
- Progression of confirmed EDSS at 6 months was reduced by 32% with masitinib and by 31% with tolebrutinib.
Plus important,
- Masitinib significantly improved manual dexterity measured by the 9-hole Peg test, in study AB07002 (-4.28; p=0.0388).
- Masitinib was shown to decrease serum neurofilament light chain (NfL) concentration in an animal model of MS and, by extension, possibly neuronal damage. [2].
- Masitinib targets not only microglia but also mast cells, which play a crucial role in progressive MS and in the experimental autoimmune encephalomyelitis (EAE) model of MS, as shown in numerous publications [3-13].
Masitinib benefits from a large database of product safety with long-term exposure in various indications. In non-oncology indications, approximately 2,200 patients received at least one dose of masitinib, more than 1,300 patients received masitinib for more than six months, and almost 1,000 patients received masitinib for more than a year.
The safety profile of BTK inhibitors shows increased liver damage, hypertension and infections, which appears to be a class effect, leaving room for alternative drugs.
In conclusion, masitinib represents a potential credible alternative to BTK inhibitors in the development of new drugs in both PPMS and nSPMS.
Professor Patrick Vermersch, MD, principal investigator of the MAXIMS study, Director of the Biology-Health Doctoral School at the University of Lille, commented: “ The data on tolebrutinib are important and pave the way for a series of new drugs in progressive forms of MS. Alongside BTK inhibitors, masitinib represents a possible serious alternative in the two forms of progressive MS, primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (nSPMS), both of which remain in need. unsatisfied medical conditions. The role of mast cells should not be overlooked in MS.”
This new development fits well with the strategy currently implemented for masitinib, as it further strengthens the scientific arguments in favor of the development of masitinib in progressive forms of MS as well as the plausibility of the results generated by the study of phase 2B/3 AB07002.
About the results of the previous phase 2B/3 study AB07002
Study AB07002 achieved its primary objective, demonstrating a statistically significant reduction in disability progression measured by the EDSS score with masitinib at a dose of 4.5 mg/kg/day (p=0.0256) [1]. This treatment effect was consistent in PPMS and nSPMS patients. Additionally, masitinib significantly reduced the risk of first EDSS progression by 42% and the risk of confirmed (3 months) EDSS progression by 37%. Masitinib also significantly reduced the risk of reaching an EDSS score of 7.0, which corresponds to a disability severe enough for the patient to use a wheelchair (p=0.0093). Product safety was consistent with the known risk profile of masitinib, with no elevated risk of infection.
[Références]
[1] Vermersch P, Brieva-Ruiz L, Fox RJ, et al. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: a randomized phase 3 clinical trial. Neurol Neuroimmunol Neuroinflamm. February 21, 2022;9(3):e1148.
[2] Hermine O, Vermersch P, et al. Masitinib limits neuronal damage, measured by serum concentration of neurofilament light chain, in a model of neurodegenerative disease of neuroimmune origin. Preprint. bioRxiv 2024.03.07.583695; doi: https://doi.org/10.1101/2024.03.07.583695
[3] Sandhu JK, Kulka M. Decoding mast cell-microglia communication in neurodegenerative diseases. Int J Mol Sci. January 22, 2021;22(3):1093.
[4] Pinke KH, et al. Should mast cells be considered therapeutic targets in multiple sclerosis? Neural Regen Res. 2020 Nov;15(11):1995-2007.
[5] Pinke KH, et al. Calming mast cells with ketotifen: a potential strategy for the treatment of multiple sclerosis? Neurotherapeutics. 2020 Jan;17(1):218-234.
[6] Brown MA, Weinberg RB. Mast cells and innate lymphoid cells: underestimated players in autoimmune demyelinating disease of the CNS. Front Immunol. 2018; 9:514.
[7] Skaper SD, Facci L, Zusso M, Giusti P. An inflammation-centered view of neurological diseases: beyond the neuronal front Cell Neurosci. 2018; 12:72.
[8] Hendriksen E, et al. Mast Cells in Neuroinflammation and Brain Disorders Neurosci Biobehav Rev. 2017;79:119-133.
[9] Elieh-Ali-Komi D, Cao Y. Role of mast cells in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Rev Allergy Immunol. 2017;52(3):436-445.
[10] Conti P, Kempuraj D. Important role of mast cells in multiple sclerosis. Mult Scler Relat Disord. 2016;5:77-80.
[11] Skaper SD, Facci L, Giusti P. Mast cells, glial cells and neuroinflammation: partners in crime?. Immunology. 2014;141(3):314-327.
[12] Skaper SD, et al. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012;26(8):3103-3117.
[13] Zappulla JP, Arock M, Mars LT, Liblau RS. Mast cells: new targets for the treatment of multiple sclerosis? J Neuroimmunol. 2002;131(1-2):5-20.
About AB Science
Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development, and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action is decisive in cell signaling. Our programs only target pathologies with a high medical need, often fatal with a low survival rate, rare or resistant to first line 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 being developed in humans in oncology, in neurodegenerative diseases, in inflammatory diseases and viral 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
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