Long-term survival analysis of masitinib in amyotrophic lateral sclerosis

• Autores: Mora, Jesus S.; Bradley, Walter G.; Chaverri, Delia; Hernández Barral, María; Mascias, Javier; Gamez, Josep; Gargiulo Monachelli, Gisella Mariana; Moussy, Alain; Mansfield, Colin D.; Hermine, Olivier; Ludolph, Albert C.
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: CLINICAL TRIALS; MASITINIB; THERAPY; TYROSINE KINASE INHIBITOR
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Background: A randomized, placebo-controlled phase III study (AB10015) previously demonstrated that orally administered masitinib (4.5 mg/kg/day) slowed rate of functional decline, with acceptable safety, in amyotrophic lateral sclerosis (ALS) patients having an ALS Functional Rating Scale-revised (ALSFRS-R) progression rate from disease onset to baseline of <1.1 points/month. Here we assess long-term overall survival (OS) data of all participants from study AB10015 and test whether a signal in OS is evident in an enriched patient population similar to that prospectively defined for confirmatory study AB19001. Methods: Survival status of all patients originally randomized in AB10015 was collected from participating investigational sites. Survival analysis (using the multivariate log-rank test and Cox proportional hazards model, with stratification factors as covariates) was performed on the intention-to-treat population and enriched subgroups, which were defined according to initial randomization, baseline ALSFRS-R progression rate and baseline disease severity. Results: A significant survival benefit of 25 months (p = 0.037) and 47% reduced risk of death (p = 0.025) was observed for patients receiving 4.5 mg/kg/day masitinib (n = 45) versus placebo (n = 62) in an enriched cohort with ⩾2 on each baseline ALSFRS-R individual component score (i.e. prior to any complete loss or severe impairment of functionality) and post-onset ALSFRS-R progression rate <1.1 (i.e. exclusion of very fast progressors) [median OS of 69 versus 44 months, respectively; hazard ratio, 0.53 [95% CI (0.31–0.92)]]. This corresponds to the population enrolled in confirmatory phase III study, AB19001. Conclusions: Analysis of long-term OS (75 months average follow-up from diagnosis) indicates that oral masitinib (4.5 mg/kg/day) could prolong survival by over 2 years as compared with placebo, provided that treatment starts prior to severe impairment of functionality.
Fil: Mora, Jesus S.. No especifíca;
Fil: Bradley, Walter G.. University of Miami; Estados Unidos
Fil: Chaverri, Delia. No especifíca;
Fil: Hernández Barral, María. No especifíca;
Fil: Mascias, Javier. No especifíca;
Fil: Gamez, Josep. Universitat Autònoma de Barcelona; España
Fil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina
Fil: Moussy, Alain. No especifíca;
Fil: Mansfield, Colin D.. No especifíca;
Fil: Hermine, Olivier. No especifíca;
Fil: Ludolph, Albert C.. Universitat Ulm; Alemania