PRESS RELEASE
AB SCIENCE PROVIDES AN UPDATE ON THE
DEVELOPMENT OF MASITINIB IN PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS
POST ECTRIMS 2024
Paris, 23 September 2024, 5.45pm 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 European Committee for Treatment and Research in
Multiple Sclerosis (ECTRIMS) 2024 conference.
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 4.5
mg/kg/day in patients with primary progressive multiple sclerosis
(PPMS) and non-active secondary progressive multiple sclerosis
(nSPMS). The study enrolls patients with Expanded Disability Status
Scale (EDSS) score between 3.0 to 6.0, progression of disease for
the last 2 years and absence of T1 Gadolinium-enhancing brain
lesions. The primary endpoint of the study is the effect of
masitinib on time to confirmed disability progression.
The recent results of tolebrutinib in non-active
secondary progressive MS presented at the ECTRIMS 2024 conference,
reinforce the scientific hypothesis that targeting microglia in
nSPMS is a valid approach. Tolebrutinib belongs to a class of drugs
that target microglia through an enzymatic target called BTK
(Bruton Tyrosine Kinase).
Masitinib also targets microglia but through a
different enzymatic target called M-CSFR1 (Macrophage Colony
Stimulating Factor Receptor-1) and generated positive results in
phase 2B (AB07002) [1], which are consistent with tolebrutinib
data.
-
EDSS progression confirmed 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
reach the conventional 5% p-value since the study was not powered
to detect a significant effect in this secondary endpoint, having
300 patients in the masitinib 4.5 or placebo arms as compared with
1100 patients in the Hercules trial).
-
EDSS progression confirmed at 6 months was reduced by 32% with
masitinib and by 31% with tolebrutinib.
Importantly,
-
Masitinib significantly improved manual dexterity measured by
9-hole Peg test, in study AB07002 (-4,28 ; p=0,0388).
-
Masitinib has shown the ability to decrease serum neurofilament
light chain (NfL) concentration in an animal model of MS, and by
extension therefore, possibly neuronal damage [2].
-
Masitinib not only targets 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 by
numerous publications [3-13].
Masitinib benefits from a large safety database
with long-term exposure across various indications. In non-oncology
indications, around 2,200 patients have received at least one dose
of masitinib, more than 1,300 patients have received masitinib for
more than six months and close to 1,000 patients have received
masitinib for more than one year.
BTK safety profiles shows increase in liver
injury, hypertension and infections which seem to be a class
effect, leaving room for alternative drugs.
As a conclusion, masitinib represents a
potential credible alternative to BTK inhibitors in the development
of new drugs both in primary and non-active secondary progressive
MS.
Professor Patrick Vermersch, MD, principal
investigator of the MAXIMS study, Director of the Doctoral School
Biology-Health of the University of Lille, commented: “Tolebrutinib
data are important and pave the way to a series of new drugs in
progressive forms of MS. Along with BTK inhibitors, masitinib
represents a serious potential alternative in the two forms of
progressive MS, primary and non-active secondary progressive MS,
which remain the two unmet medical needs. The role of mast cells is
not to be neglected in MS”.
This new development fits well the strategy
currently implemented for masitinib, as it further strengthens the
scientific rationale for the development of masitinib in
progressive forms of MS as well as the plausibility of the results
generated with phase 2B/3 study AB07002.
About the results of the previous phase
2B/3 study AB07002Study AB07002 met its primary analysis
endpoint, demonstrating a statistically significant reduction in
cumulative change on EDSS with masitinib 4.5 mg/kg/day (p=0.0256)
[1]. This treatment-effect was consistent for PPMS and nSPMS. In
addition, masitinib significantly reduced the risk of first
disability progression by 42% and the risk of confirmed (3 months)
disability progression by 37%. Masitinib also significantly reduced
the risk of reaching an EDSS score of 7.0, corresponding to
disability severe enough that the patient is restricted to a
wheelchair (p=0.0093). The product's safety was consistent with the
known risk profile of masitinib, with no elevated risk of
infection.
[References]
[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. 2022 Feb 21;9(3):e1148.
[2] Hermine O, Vermersch P, et al. Masitinib
limits neuronal damage, as measured by serum neurofilament light
chain concentration, in a model of neuroimmune-driven
neurodegenerative disease. 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. 2021 Jan 22;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 Down Mast Cells
with Ketotifen: A Potential Strategy for Multiple Sclerosis
Therapy? Neurotherapeutics. 2020 Jan;17(1):218-234.
[6] Brown MA, Weinberg RB. Mast Cells and Innate
Lymphoid Cells: Underappreciated Players in CNS Autoimmune
Demyelinating Disease. Front Immunol. 2018;9:514.
[7] Skaper SD, Facci L, Zusso M, Giusti P. An
Inflammation-Centric View of Neurological Disease: Beyond the
Neuron 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,
glia 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 multiple sclerosis therapy?. J
Neuroimmunol. 2002;131(1-2):5-20.
About AB ScienceFounded 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 are
key in signaling pathways within cells. Our programs target only
diseases with high unmet medical needs, often lethal with short
term survival or rare or refractory to previous line of treatment.
AB Science has developed a proprietary portfolio of molecules and
the Company’s lead compound, masitinib, has already been registered
for veterinary medicine and is developed in human medicine in
oncology, neurological diseases, inflammatory diseases and viral
diseases. The company is headquartered in Paris, France, and listed
on Euronext Paris (ticker: AB).
Further information is available on AB Science’s
website: www.ab-science.com.
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- CP UPDATE ECTRIMS 2024. VEng VF
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