» AB Science: US FDA approval to initiate a confirmatory phase 3 study with masitinib in Alzheimer’s disease MyPharma Editions

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AB Science: US FDA approval to initiate a confirmatory phase 3 study with masitinib in Alzheimer's disease

Posted on Tuesday, November 22, 2022

AB Science has just announced that its Phase III clinical study (AB21004) in mild to moderate Alzheimer’s disease has been approved by the US Food and Drug Administration (FDA). This decision follows similar authorizations received from several European countries, including the French Medicines Agency (ANSM).

Professor Olivier Hermine, President of the Scientific Committee of AB Science and member of the Academy of Sciences, declared: “The authorization to launch this confirmatory study issued by the main international health agencies shows that masitinib is considered as a credible drug candidate in Alzheimer’s disease in the largest and therefore strategically most important population, which corresponds to patients with mild and moderate dementia. This population has proven to be particularly difficult for clinical studies over the past twenty years and still represents a very important medical need. Based on its mechanism of action, we believe that masitinib may act on disease progression due to its ability to convert microglia and mast cells from a neurodegenerative to a neuroprotective phenotype in Alzheimer’s disease. Alzheimer’s as well as in other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and progressive forms of multiple sclerosis”.

The AB21004 study is a phase 3 randomized double-blind study aimed at evaluating the safety and efficacy of masitinib in patients with mild or moderate Alzheimer’s disease, in combination with reference treatments, namely inhibitors cholinesterase and/or memantine. The study should recruit 600 patients whose clinical diagnosis of mild or moderate Alzheimer’s disease has been confirmed, which corresponds to an MMSE (Mini Mental State Examination) score between 14 and 25, inclusive.

The objective of the AB21004 study is to confirm the results of the first phase 2B/3 study, AB09004, which showed that masitinib administered at a dose of 4.5 mg/kg/day significantly slowed cognitive deterioration by compared to placebo and also reduced the loss of functional ability in activities of daily living in the target population of patients with Alzheimer’s disease. The main endpoint of the study will be to assess the effect of masitinib on the change in the ADCS-ADL score and the ADAS-Cog-11 score, compared to inclusion.

The positioning of masitinib is different from that of other drugs developed in Alzheimer’s disease, such as lecanemab, aduhelm, donanemab and crenenzumab, which target the early stages of Alzheimer’s disease, including very severe dementia. mild, prodromal or asymptomatic Alzheimer’s disease (ie with an MMSE score >22 and up to 30, an MMSE score of 27-30 corresponding to normal cognitive functions).

Masitinib’s mechanism of action is also different from many other drugs being developed in Alzheimer’s disease and may be complementary in that masitinib targets microglia and mast cells to generate a disease-modifying neuroprotective effect, so that lecanemab, aduhelm, donanemab and crenenzumab are anti-amyloid antibodies that aim to eliminate toxic aggregates of beta-amyloid (Aβ).

Also, masitinib is an orally administered tyrosine kinase whereas anti-amyloid antibodies are administered by injection.

Dr. Jeffrey Cummings, Director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas, USA, said: “We are very pleased to initiate this international phase III study with masitinib in the United States, especially since the therapeutic options are very limited for patients with mild or moderate Alzheimer’s disease. The trial (AB21004) aims to confirm the results observed in the previous phase 2B/3 study (AB09004), which provided initial proof of the efficacy and good tolerance of masitinib in Alzheimer’s disease”.

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 effective therapies of Alzheimer’s disease. Forehead. Drug Chem. Wink. 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 disease. Ann Transl Med. 2018;6(10):176.

Source and visual: AB Science

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