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Masitinib delivers strike to Lou Gehrig’s disease
PARIS—Taking one baby step at a time toward finding a cure for the rare disorder known as amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, French pharma AB Science SA has announced preclinical data showing a protective effect of masitinib on the peripheral nervous system in an ALS model. The study, published Oct. 19 in the peer-reviewed Journal of Clinical Investigation Insight, sheds light on how masitinib slows down the disease that kills most of its victims within five years of diagnosis.
Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases and in certain diseases of the central nervous system.
Classified as a motor neurone disease, ALS causes the death of neurons that control voluntary muscles. Approximately 50,000 people with ALS live in the European Union and the United States, with more than 16,000 new cases diagnosed each year. Almost 80 percent of ALS patients die within five years and 90 percent die within 10 years, according to the World Health Organization. There is research predicting that worldwide prevalence of ALS, currently estimated at 235,000, will see a projected 69-percent increase by the year 2040.
That’s why finding an effective treatment—or cure—for ALS is a critical, urgent need.
The research study by AB Science links increased mast cell activity to the degeneration of neuromuscular junctions and paralysis progression in a relevant model of ALS. Its findings represent a novel pathogenic mechanism in ALS that is shown to be therapeutically targeted by masitinib.
“These findings represent a significant mechanism of action for masitinib, which may have clinical therapeutic relevance for ALS,” states Prof. Luis Barbeito, head of the Neurodegeneration Laboratory (Institut Pasteur in Montevideo, Uruguay) and senior author of the journal article. “Taken together with our previously published preclinical finding, we now have evidence that masitinib generates a protective effect via two independent mechanisms of action involving immune cells interacting with motor neurons, with one predominantly impacting on the central nervous system via targeting deleterious microglial cells in the brain. The other mechanism impacts on the peripheral nervous system via prevention of neuromuscular junction denervation.”
The potential for masitinib as a treatment for neurodegenerative disease was first demonstrated in positive Phase 2 studies for Alzheimer’s disease and progressive forms of multiple sclerosis, Barbeito says. Preclinical research from his team provided the first ALS-specific proof of concept, including observation of an unprecedented protective effect for masitinib in ALS rat models, with respect to other studies found in the scientific literature.
Prof. Olivier Hermine, president of the scientific committee of AB Science, says: “Regarding the treatment effect observed in humans, we have seen from the results of a Phase 3 clinical trial that masitinib as an add-on therapy to riluzole significantly delayed disease progression when compared with riluzole treatment alone, in a number of clinically relevant measures of the disease.”
The Phase 3 trial also showed a “significant slowing of deterioration in the ALS Functional Rating Scale-Revised score (primary endpoint), as well as slowing of deterioration in measures of quality of life (ALSAQ-40), respiratory function and disease progression (survival-to-event analysis),” Hermine adds. “The objective of developing masitinib in ALS is to provide patients with a better treatment option than what is currently available, ideally delaying disease progression and improving their quality of life.”
Masitinib has already been registered for veterinary medicine in Europe and in the United States and is being explored in 12 Phase 3 indications in human medicine in metastatic prostate cancer, metastatic pancreatic cancer, relapsing metastatic colorectal cancer, relapsing metastatic ovarian cancer, gastrointestinal stromal tumor, metastatic melanoma, mastocytosis, severe asthma, Alzheimer’s disease and progressive forms of multiple sclerosis—as well as ALS.