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Abstract
Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer-term efficacy and safety. Patients given edaravone in the first 24-week phase III study (Cycles 1–6) were randomised to edaravone (E-E) or placebo (E-P) in the subsequent 24-week double-blind period (Cycles 7–12). Patients given placebo in phase III were switched to edaravone (P-E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13–15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy-expected subpopulation (EESP) defined by post-hoc analysis of the first phase III study. The least-squares mean and standard error of the intergroup difference (E-E vs. E-P) of change in the ALSFRS-R score from Cycles 7–12 was 1.16 ± 0.93 (p = 0.2176) in the FAS, and 1.85 ± 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E-E group throughout Cycles 1–15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E-E than in E-P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.
Acknowledgements
We thank all participating patients and their family members, and participating staff at all study sites; Contract Clinical Research Associates; Teresa Oblak of Covance Market Access, Inc., for editorial assistance; Richard Steele of WRS Steele Scientific and Technical Editing for proofreading the manuscript; Koji Takei and Kikumi Tsuda of Mitsubishi Tanabe Pharma Development America for critical review of the manuscript.
Declaration of interests
Mr. Abe received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Itoyama received speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Tsuji received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Sobue received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation, and serves on the scientific advisory board for the Kanae Science Foundation for the Promotion of Medical Science, Naito Science Foundation, and as an advisory board member of Brain, an editorial board member of Degenerative Neurological and Neuromuscular Disease, the Journal of Neurology, and Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, and has received funding from several Japanese government agencies. Mr. Aoki received travel funds, speaker honoraria, and fees for conducting and consulting on pharmacological testing of edaravone in a rat ALS model, from Mitsubishi Tanabe Pharma Corporation, and has received research grants from several Japanese government agencies, including an Intramural Research Grant for Neurological Psychiatric Disorders from the National Center of Neurology and Psychiatry (NCNP). Mr. Doyu received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Hamada is a consultant for Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Kowa Company. Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Maruho Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mochida Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Pharmaceutical Co., Ltd. and Mitsubishi Tanabe Pharma Corporation. Mr. Tanaka, Mr. Akimoto, Ms. Nakamura, Mr. Naito, Ms. Murakami, Mr. Takahashi and Mr. Kondo are employees of Mitsubishi Tanabe Pharma Corporation. Mr. Yoshino received travel funds and speaker honoraria from, had co-owned a patent with, and is a consultant for Mitsubishi Tanabe Pharma Corporation. This study was funded by Mitsubishi Tanabe Pharma Corporation.
Open access publication of this article and editorial support were funded by Mitsubishi Tanabe Pharma America, Inc.