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Abstract
Our first phase III study failed to demonstrate efficacy of edaravone for amyotrophic lateral sclerosis (ALS) compared to placebo. Here, we performed post-hoc subgroup analysis to identify a subgroup in which edaravone might be expected to show efficacy. We focussed on two newly defined subgroups, EESP and dpEESP2y. The EESP was defined as the efficacy-expected subpopulation with % forced vital capacity of ≥80%, and ≥2 points for all item scores in the revised ALS functional rating scale (ALSFRS-R) score before treatment. The dpEESP2y was defined as the greater-efficacy-expected subpopulation within EESP having a diagnosis of ‘definite’ or ‘probable’ ALS according to the El Escorial revised Airlie House diagnostic criteria and onset of disease within two years. The primary endpoint of the post-hoc analysis was the change in the ALSFRS-R score during the 24-week treatment period. The intergroup differences of the least-squares mean change in the ALSFRS-R score ± standard error during treatment were 0.65 ± 0.78 (p = 0.4108) in the full analysis set, 2.20 ± 1.03 (p = 0.0360) in the EESP, and 3.01 ± 1.33 (p = 0.0270) in the dpEESP2y. Edaravone exhibited efficacy in the dpEESP2y subgroup. A further clinical study in patients meeting dpEESP2y criteria is warranted.
Acknowledgements
We thank all participating patients, their family members, and participating staff at all study sites; Teresa Oblak of Covance Market Access, Inc., for editorial assistance; Aya Tokaji and Marika Ogasawara of MDS-CMG Inc., for publication 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.
The Edaravone (MCI-186) ALS 16 Study Group: Site investigators
The Edaravone (MCI-186) ALS 16 Study Group investigators are as follows.
Hidenao Sasaki, Hokkaido University Hospital; Asako Takei and Isao Yamashita, Hokuyukai Neurological Hospital; Takashi Imai, National Hospital Organisation Miyagi National Hospital; Imaharu Nakano††, Jichi Medical School Hospital; Koichi Okamoto, Gunma University Hospital; Yuichi Maruki, Saitama Center of Neurology and Psychiatry; Shuichi Mishima and Jin Nishimiya, Kohnodai Hospital, National Center for Global Health and Medicine; Yasuo Iwasaki, Toho University Omori Medical Center; Mineo Yamazaki, Nippon Medical School Hospital; Yuji Takahashi, The University of Tokyo Hospital; Mieko Ogino and Yutaka Ogino, Kitasato University East Hospital; Masafumi Ogawa, National Center of Neurology and Psychiatry (NCNP); Tetsumasa Kamei, Shonan Fujisawa Tokushukai Hospital; Tsuyoshi Uchiyama, Seirei Hamamatsu General Hospital; Hirohisa Watanabe, Nagoya University Hospital; Yasumasa Kokubo, Mie University Hospital; Hideyuki Sawada, National Hospital Organisation Utano Hospital; Takanori Hazama, Osaka General Medical Center; Fumiharu Kimura, Osaka Medical College Hospital; Harutoshi Fujimura, National Hospital Organisation Toneyama National Hospital; Hirofumi Kusaka, Kansai Medical University Takii Hospital; Tsukasa Hashimoto, National Hospital Organisation Ehime National Hospital; Takeshi Yamada, Yuji Kanamori and Kenji Yamasaki, Saiseikai Fukuoka General Hospital; Shizuma Kaku, Fukuoka Tokushukai Medical Center; Hitoshi Kikuchi, Murakami Karindoh Hospital; Shigehiro Imamura, National Hospital Organisation Kumamoto Saishunso National Hospital; Seiichiro Sugimoto and Masahiko Kishi, National Hospital Organisation Miyazaki Higashi Hospital. ††Deceased.
Declaration of interest
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, and 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. Dr. 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. Togo, Mr. Tanaka, Mr. Akimoto, Ms. Nakamura, Mr. Takahashi and Mr. Kondo are employees of Mitsubishi Tanabe Pharma Corporation. Mr. Yoneoka is an employee of and had co-owned a patent with 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.