Alzheimer’s disease is an irreversible, neurodegenerative disorder leading to disabling impairment of memory and cognitive skills. Alzheimer’s disease is the most common cause of dementia among older adults. Masitinib is currently investigated in mild to moderate forms of Alzheimer’s disease.
Currently, there is no satisfactory treatment for mild and moderate forms of Alzheimer’s disease. Therefore, this remains an area of significant unmet medical need.
Masitinib is positioned in the treatment of mild and moderate Alzheimer’s disease, that is to say, for patients already having clinical signs of dementia. Masitinib is not positioned in prodromal (pre-symptomatic) forms of the disease.
The rationale for evaluating masitinib in Alzheimer’s disease is based on masitinib’s inhibition of the c-Kit, Lyn, Fyn and CSF1R kinases.
The number of patients targeted by masitinib amounts to 5,000,000 in Europe and in the US.
AB Science reported positive Phase 2A proof of concept results with masitinib in Alzheimer’s disease. In this study, masitinib showed a decrease of the decline of cognitive function and an improvement in daily living activities. The results of the study have been published in the Alzheimer’s Research & Therapy.
AB Science completed a phase 2B/3 study to assess the safety and efficacy of masitinib in patients with confirmed mild to moderate Alzheimer’s disease. In this study, masitinib is given as add-on therapy to cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine.
The study demonstrated that masitinib 4.5 mg/kg/day generated a significant treatment effect compared with the control arm (on the primary endpoint of change from baseline in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), an instrument that measures the effect on cognition and memory (p=0.0003).
The study also demonstrated that masitinib 4.5 mg/kg/day generated a significant change from baseline in Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) score, an instrument that assesses self-care and activities of daily living (p= 0.0381).
There were significantly fewer patients reaching severe dementia stage (MMSE<10) with masitinib 4.5 mg/kg/day compared with placebo after 24 weeks of treatment (p-value= 0.0446).
The safety of masitinib 4.5 mg/kg/day was acceptable and consistent with the known tolerability profile for masitinib.
AB Science received authorization to initiate a confirmatory phase III study evaluating masitinib in patients with mild to moderate Alzheimer’s Disease. The study will enroll 600 patients with confirmed clinical diagnosis of mild and moderate Alzheimer’s disease, corresponding to an Activities of Daily Living (ADCS-ADL) score of less than 73 and a Mini Mental State Examination (MMSE) score of between 14 to 25, inclusive. The objective of study AB21004 is to confirm treatment effect with masitinib 4.5 mg/kg/day as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer’s disease. The primary endpoint of the study will be to evaluate the effect of masitinib on absolute change from baseline in ADCS-ADL score and in ADAS-Cog-11.