AB Science SA, a pharmaceutical company focused on research, advancement and commercialization of protein kinase inhibitors (PKIs) announced that the external Data and Safety Monitoring Board (DSMB) recommended the company’s phase 3 study of masitinib in amyotrophic lateral sclerosis (ALS) be continued. The decision was supported by the drug’s latest safety reports.
The current phase 3 clinical trial is a multicentered, double-blinded, randomized and international study that aims to compare the efficacy and the safety of masitinib with a placebo, in order to treat patients suffering from amyotrophic lateral sclerosis. The investigational treatment is given to patients that have been treated previously with a known and stable dose of riluzole. Researchers measured the efficacy of the compound after 48 weeks of treatment, using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-Revised). The outcomes of the study confirm that there are no safety concerns regarding masitinib combined with riluzole for a period of one year post-treatment.
Olivier Hermine, from AB Science, explained in a press release: “In this study, we assume that mast cells, which are key immune cells, actively participate to the pathogenesis of ALS, through the release of mediators that sustain the inflammatory network of the central nervous system. Mast cells, which are present in large quantities in the brain and in the spinal cord, could also influence the survival and function of motor neurons, and thus participate to the pathophysiology of ALS. Since masitinib is a selective inhibitor of c-Kit and Lyn, two kinases that play a major role in the survival and activation of mast cells, it may lead to positive effects on the symptoms of the pathology.”
Dr. Luis Barbeito from the Institut Pasteur de Montevideo, Uruguay, commented: “We completed several studies in animal models suggesting that masitinib might offer therapeutic benefits in ALS patients alone or in combination with riluzole. Notably, masitinib demonstrated in transgenic ALS murine model a delay in the onset of symptoms, improvement in grip strength, reduction in weight loss and a trend of increased survival. Masitinib also prevented the increase in tryptase expression – a marker of inflammation, and perivascular mast cell number, and prevented motoneuron pathology and death in a murine model for ALS, thus suggesting the implication of mast cells. We are currently conducting additional animal experiments to better elucidate the precise mechanism of action of masitinib in this disease, yet we believe the body of evidence we already have strongly supports the on-going phase 3 study in ALS.”