Efficacy of Radicava® IV (intravenous edaravone) in subjects with differing trajectories of disease progression in amyotrophic lateral sclerosis: Use of a novel statistical approach for post hoc analysis of a pivotal phase 3 clinical trial.

Introduction: Subjects with amyotrophic lateral sclerosis (ALS) treated with Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA], hereafter "MTPA IV edaravone") in Study MCI186-19 had a significantly slower physical functional decline vs placebo-treated subjects as measured by the revised ALS Functional Rating Scale (ALSFRS-R) and analyzed by the linear mixed model for repeated measures (MMRM). This Study 19 post hoc analysis of MTPA IV edaravone-treated and placebo-treated subjects evaluated linear and nonlinear latent class mixed models defining trajectories based on identifying the model with the lowest Bayesian information criterion. The best model differentiated 4 nonlinear trajectories in ALS subjects. ALSFRS-R total score in MTPA IV edaravone-treated and placebo-treated subjects was evaluated for these 4 nonlinear latent class trajectory groups.

Methods: Disease trajectories of MCI186-19 MTPA IV edaravone-treated or placebo-treated ALS subjects who completed the double-blind period were investigated using latent class analysis (LCA) statistical models to identify potential unique nonlinear ALSFRS-R disease trajectories.

Results: ALSFRS-R trajectories revealed 4 unique nonlinear trajectory latent classes per treatment group in MTPA IV edaravone-treated and placebo-treated ALS subjects completing the MCI186-19 double-blind period. Latent classes 2-4 had statistically significant slowing of ALSFRS-R total score decline in the predicted nonlinear trajectories of MTPA IV edaravone-treated vs placebo-treated ALS subjects.

Conclusions: This post hoc analysis suggests MTPA IV edaravone treatment results in slower ALSFRS-R decline vs placebo in most predicted nonlinear trajectories. LCA is a novel approach that may benefit future trial analyses.