AB Science Gains European Approval for Phase 3 Masitinib Study in ALS Treatment

AB Science SA, a pharmaceutical company focused on developing protein kinase inhibitors, has received authorization from Spain, Greece, and Slovenia to launch its confirmatory Phase 3 clinical trial, study AB23005, for masitinib in treating amyotrophic lateral sclerosis (ALS). This milestone follows the European Medicines Agency’s (EMA) validation of the study’s harmonized protocol and approval from the U.S. Food and Drug Administration (FDA), paving the way for the trial to commence in Europe and the United States.

The AB23005 study, a multicenter, randomized, double-blind, placebo-controlled trial, will evaluate masitinib (4.5 mg/kg/day combined with riluzole) against a placebo with riluzole over 48 weeks. It aims to confirm the drug’s efficacy and safety in 408 ALS patients with normal disease progression (functional decline of less than 1.1 points per month on the ALSFRS-R scale) and no complete loss of function. The study design, which includes U.S. patients using edaravone, has been endorsed by European health authorities, ensuring a focus on patients most likely to benefit from masitinib.

Professor Albert Ludolph, MD, PhD, from the University of Ulm, Germany, and principal investigator, highlighted the trial’s promise: “The AB23005 study is built on compelling data from the earlier Phase 2B/3 AB10015 trial, which showed a significant survival benefit of several months in this patient group, alongside preclinical evidence of masitinib’s impact on ALS biomarkers like neurofilaments by targeting mast cells and microglia.”

The earlier AB10015 study demonstrated masitinib’s effectiveness in a similar patient subgroup, achieving a statistically significant result (p=0.0290) on the FDA-recognized CAFS endpoint, with a median survival increase of 12 months. The new study doubles the sample size to approximately 200 patients per treatment arm to enhance statistical power and increase the likelihood of success.

Masitinib’s mechanism of action, which targets mast cells and microglia to preserve neuromuscular function, has been validated in preclinical models, including SOD1G93A mice and zebrafish expressing TDP-43 mutations. It has also shown a reduction in neurofilament light (NfL) levels, a key ALS biomarker, and improved motor performance in preclinical settings.

AB Science has secured intellectual property protection for masitinib in ALS treatment until 2037, with potential extensions to 2042 in some regions. The drug has also been granted orphan drug designation by the EMA and FDA, offering market exclusivity of 10 and 7 years, respectively, upon approval.

With these approvals, AB Science is poised to advance its mission to deliver innovative therapies for ALS, a devastating neurodegenerative disease, bringing hope to patients worldwide.