PRESS RELEASE
AB SCIENCE RECEIVES FIRST AGENCIES AUTHORIZATIONS TO INITIATE CONFIRMATORY PHASE 3 CLINICAL STUDY WITH MASITINIB IN THE TREATMENT OF ALZHEIMER’S DISEASE
Paris, October 10th 2022, 6pm CET
AB Science SA (Euronext – FR0010557264 – AB) as we speak broadcasts that the first authorizations have been acquired to provoke its part 3 confirmatory research (AB21004) evaluating masitinib in sufferers with gentle to average Alzheimer’s Disease (AD) from the French Medicine Agency (ANSM) along with AEMPS (Spain company) and EOF (Greece company).
Study AB21004 is a randomized, double-blind part 3 research to consider the protection and efficacy of masitinib in sufferers with gentle to average Alzheimer’s illness, as an add-on remedy to commonplace of care, cholinesterase inhibitors and/or memantine. The research will enroll 600 sufferers with confirmed medical analysis of gentle and average Alzheimer’s illness, corresponding to an Activities of Daily Living (ADCS-ADL) rating of lower than 73 and a Mini Mental State Examination (MMSE) rating of between 14 to 25, inclusive.
The goal of research AB21004 is to verify remedy impact with masitinib 4.5 mg/kg/day as an adjunct to cholinesterase inhibitor and/or memantine in sufferers with mild-to-moderate Alzheimer’s illness. The main endpoint of the research might be to consider the impact of masitinib on absolute change from baseline in ADCS-ADL rating and in ADAS-Cog-11.
The positioning of masitinib is totally different from different Alzheimer’s illness medicine reminiscent of lecanemab, aduhelm, donanemab and crenenzumab, which goal the earliest phases of the AD continuum, together with very gentle dementia, prodromal or asymptomatic Alzheimer’s illness, MMSE>22 and up to 30, whereas sufferers with MMSE 27-30 have regular cognitive capabilities.
The mechanism of motion of masitinib can also be totally different from different medicine being developed for Alzheimer’s illness and presumably complementary within the sense that masitinib targets microglia and mast cells to ship a illness modifying neuro protecting impact, whereas lecanemab, aduhelm, donanemab, and crenenzumab are anti-amyloid antibodies that goal to eradicate poisonous amyloid-beta (Aβ) aggregates.
Furthermore, masitinib is an orally administered tyrosine kinase whereas the aforementioned anti-amyloid antibody medicine are administered by way of injection.
Professor Bruno Dubois, MD, principal investigator of the research and Professor of Neurology at Sorbonne University, France commented, “We are very excited to initiate this confirmatory phase III study with masitinib in Alzheimer’s disease. There is a vacuum of treatment options for patients with mild or moderate Alzheimer’s disease. The results from first phase 2B/3 study, AB09004, were very encouraging, especially considering this is a difficult to treat patient population. First, we found the optimal dose out of the three tested. Second, masitinib administered at 4.5 mg/kg/day, significantly slowed cognitive deterioration relative to placebo and also showed reduced loss of functional ability in activities of daily living. Of equal importance, it was shown that the safety of masitinib when administered as an adjunct to cholinesterase inhibitor and/or memantine was in line with its known safety profile and not worsened in this aged population.”
Professor Olivier Hermine, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France, stated: “With these first company authorizations, AB Science has now launched in the third key indication with masitinib in its confirmatory program; these being amyotrophic lateral sclerosis, progressive types of a number of sclerosis, and now Alzheimer’s illness. Masitinib is a platform program to deal with neurodegenerative illnesses primarily based on its distinctive mechanism of motion concentrating on microglia and mast cells, important cells which can be thought to contribute to the neurodegenerative course of and if correctly managed contribute to neuro safety ».
About the outcomes from earlier part 2B/3 AB09004
Study AB09004 was the first profitable part 2B/3 randomized trial in mild-to-moderate Alzheimer’s illness of a drug concentrating on innate immune cells of the neuroimmune system. Masitinib at 4.5 mg/kg/day confirmed important profit over placebo in accordance to the first evaluation, with a suitable security profile.
Primary efficacy evaluation (primarily based on a number of endpoints, every examined at a significance degree of two.5%) was the least-squares imply change from baseline to week-24 in both the 11-item Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog), or the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL).
Results confirmed that masitinib can generate a major remedy impact relative to placebo within the main endpoint of change from baseline in ADAS-Cog, an instrument that measures the impact on cognition and reminiscence. Specifically, masitinib 4.5 mg/kg/day (n=182) confirmed important profit relative to placebo (n=176), with a respective change in ADAS-cog from baseline of -1.46 (representing an total enchancment in cognition) versus +0.69 (representing elevated cognitive deterioration); a corresponding ADAS-cog between-group distinction of -2.15 (97.5percentCI [-3.48, -0.81]), p=0.0003.
It was additionally seen that masitinib generated a non-significant pattern in direction of improved total operate relative to placebo as measured by the ADCS-ADL rating, an instrument that assesses self-care and actions of day by day dwelling. Specifically, masitinib 4.5 mg/kg/day confirmed a change in ADCS-ADL from baseline of +1.01 (representing an total useful enchancment) versus -0.81 for placebo (representing elevated useful deterioration); a corresponding ADCS-ADL between-group distinction of +1.82 (97.5percentCI [(-0.15, 3.79]), p=0.038.
The security of masitinib as an adjunct to cholinesterase inhibitor and/or memantine was acceptable and in step with its identified tolerability profile. It is noteworthy that this result’s within the context of a relative aged inhabitants (common age of about 73 years) with comorbidities. The incidence of sufferers having a minimum of one treatment-emergent hostile occasion (AE) after 24 weeks of remedy was 87% for masitinib 4.5 mg/kg/day versus 77.5% for the placebo-control group. This corresponds to an incidence price ratio (masitinib/placebo) of 1.1. The incidence of extreme AE for masitinib 4.5 mg/kg/day was 26.5% versus 19.3% within the placebo-control group, corresponding to an incidence price ratio of 1.4.
About masitinib’s mechanism of motion in Alzheimer’s illness
Masitinib (AB1010) is an oral tyrosine kinase inhibitor that has demonstrated neuroprotective motion in neurodegenerative illnesses by way of inhibition of mast cell and microglia/macrophage exercise, presumably by switching the neuroimmune system from a neurotoxic state in direction of a neuroprotective state via reworking of the neuronal microenvironment. Mast cells, macrophages and microglia are kinds of innate immune cells which can be current within the central nervous system, and for which there’s a rising physique of proof implicating them within the pathophysiology of neurodegenerative illnesses reminiscent of Alzheimer’s illness, progressive types of a number of sclerosis and amyotrophic lateral sclerosis (ALS).
The rationale to use masitinib in Alzheimer’s illness sufferers is supported by preclinical proof demonstrating that the pharmacological motion of masitinib in mast cells can restore regular spatial studying efficiency in a mouse mannequin of Alzheimer’s illness and promotes restoration of synaptic markers [1].
Despite a long time of intensive analysis, the overwhelming majority of human trials (predominantly testing amyloid-based therapeutics) have failed to exhibit medical efficacy. This underscores a necessity for modern, non-amyloid primarily based approaches, together with therapies that modulate the neuroimmune response in Alzheimer’s illness, which has been implicated within the pathophysiology of the illness [2–6].
References :
[1] Li T, Martin E, Abada YS, et al. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer’s Disease. J Alzheimers Dis. 2020;76(4):1339-1345.
[2] Long JM, Holtzman DM. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell. 2019;179(2):312-339
[3] Sandhu JK, Kulka M. Decoding Mast Cell-Microglia Communication in Neurodegenerative Diseases. Int J Mol Sci. 2021;22(3):1093.
[4] Klegeris A. Microglial targets for efficient therapies of Alzheimer’s illness. Front. Drug Chem. Clin. Res. 2020;3:1–4
[5] Tchessalova D, Posillico CK, Tronson NC. Neuroimmune Activation Drives Multiple Brain States. Front Syst Neurosci. 2018;12:39.
[6] Li JW, Zong Y, Cao XP, Tan L, Tan L. Microglial priming in Alzheimer’s illness. Ann Transl Med. 2018;6(10):176.
About AB Science
Founded in 2001, AB Science is a pharmaceutical firm specializing within the analysis, improvement and commercialization of protein kinase inhibitors (PKIs), a category of focused proteins whose motion are key in signaling pathways inside cells. Our applications goal solely illnesses with excessive unmet medical wants, usually deadly with brief time period survival or uncommon or refractory to earlier line of remedy.
AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medication and is developed in human medication in oncology, neurological illnesses, inflammatory illnesses and viral illnesses. The firm is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB).
Further info is on the market on AB Science’s web site:
www.ab-science.com.
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