Sustained Efficacy for up to 12 Months in an Active Extension of a Phase III Study of Edaravone (MCI-186) for Treatment of Amyotrophic Lateral Sclerosis (ALS) (P3.190)

Abstract

Objective: To evaluate efficacy and safety of edaravone for an additional 24 weeks via an active extension study Background:In a preceding 24-week, double-blind (DB) study (Edaravone MCI-186-J19/NCT01492686) edaravone showed efficacy versus placebo as measured by change in ALS Functional Rating Scale-Revised (ALSFRS-R) and ALS Assessment Questionnaire (ALSAQ40) scores in ALS patients with greater functionality at baseline. Design/Methods:Patients completing DB phase were eligible to continue into the extension, consisting of an additional 6 cycles of 60-mg once-daily edaravone. Each cycle consisted of 10-days of treatment over 2 weeks followed by a 14-day drug-free period, for a total of 48 weeks. Main efficacy endpoints were changes in ALSFRS-R and ALSAQ40 scores. Safety endpoints included adverse events (AEs) and laboratory tests. Results:58 patients previously on placebo were switched to edaravone (P-E), and 65 patients continued on edaravone (E-E) after completion of the DB phase. The baseline to 12-month between-group difference (E-E vs P-E groups) in adjusted mean (±SE) scores was 4.17±1.40(P=0.004) for ALSFRS-R, and -10.71±4.51(P=0.020) for ALSAQ40. Twelve and 18 patients discontinued from the E-E and P-E groups, respectively: majority due to patient request (43[percnt]) or respiratory support requirement (33[percnt]). Incidences of AEs were 81.5[percnt] and 82.8[percnt] for E-E and E-P groups respectively. Incidence of serious AEs was 26.2[percnt] in the E-E group and 39.7[percnt] in the P-E group. Two patients in the E-E group died due to AEs of respiratory failure/disorder, and 4 died in the P-E group due to respiratory failure/disorder, pneumonia aspiration, and stress cardiomyopathy. Conclusion:Patients initially randomized to edaravone (versus placebo), and who continued edaravone treatment for up to12 months, showed a sustained efficacy advantage compared to those who began on placebo in DB and switched to edaravone 6 months later. Early treatment with edaravone appears to improve efficacy and quality of life in this population of ALS patients.

Disclosure: Dr. Palumbo has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Sakata has received personal compensation for activities with the Mitsubishi Tanabe Pharmaceutical Corporation. Dr. Tanaka has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Akimoto has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation.