The European Medicines Agency (EMA) has confirmed its negative opinion regarding the conditional marketing authorization of masitinib for the treatment of amyotrophic lateral sclerosis (ALS) in the European Union. This decision, made by the Committee for Medicinal Products for Human Use (CHMP), follows AB Science's request for a re-examination of the initial negative opinion issued in June 2024.
Details of the Decision
AB Science sought re-examination based on data from the AB10015 Phase 2/3 clinical study (NCT02588677), which evaluated masitinib in combination with Rilutek (riluzole) in 394 adults with ALS. The primary endpoint was to assess whether masitinib could slow disease progression, measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
Alain Moussy, CEO and co-founder of AB Science, expressed gratitude to patients and physicians who supported the re-examination process. "We did all these efforts for the patients. We are convinced that masitinib is a promising drug when we see patients from the study surviving with the drugs for more than 10 years in our compassionate use program," Moussy stated.
Concerns and Analysis
The application was primarily supported by data from a subgroup of patients with normal-progressing disease (defined as a monthly decline in ALSFRS-R score of less than 1.1 points). In this group, the 4.5 mg/kg dose of masitinib showed a 27% slower disease progression compared to placebo. However, the CHMP raised concerns regarding the analysis of this subgroup and another subgroup of mild to moderate ALS patients, where greater benefits were observed.
A Scientific Advisory Group for Neurology (SAG-N) reviewed the data and agreed that the 1.1 points per month ALSFRS-R decline cutoff was acceptable for distinguishing between normal and fast progressors, provided it was pre-specified before the trial began. This supports the design of the ongoing AB19001 Phase 3 clinical trial (NCT03127267), which uses the same cutoff.
Next Steps for AB Science
AB Science has decided not to pursue reconsideration in Canada after Health Canada classified key analyses as new data, which is not permitted during the reconsideration process. Instead, the company will focus on a confirmatory Phase 3 program to seek full approval for masitinib in ALS.
"Now AB Science objective is to focus on the confirmatory phase 3 program of masitinib in ALS to reach full approval," said Moussy.
