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Clinical Trial
. 2025 Sep;72(3):433-442.
doi: 10.1002/mus.28448. Epub 2025 Jun 6.

Efficacy and Safety of Once Daily Dosing vs. Approved On/Off Dosing of Edaravone Oral Suspension Up to 48 Weeks in Patients With Amyotrophic Lateral Sclerosis (Study MT-1186-A02)

Jeffrey Rothstein  1 , Angela Genge  2 , Shari De Silva  3 , Lorne Zinman  4 , Marvin Chum  5 , Adriano Chio  6 , Gen Sobue  7   8 , Masashi Aoki  9 , Hiide Yoshino  10 , Manabu Doyu  11 , Daniel Selness  12 , Vesna Todorovic  13 , Nissim Sasson  14 , Manabu Hirai  12 , Fumihiro Takahashi  12 , Alejandro Salah  12 , Art Wamil  12 , Stephen Apple  12
Affiliations
Clinical Trial

Efficacy and Safety of Once Daily Dosing vs. Approved On/Off Dosing of Edaravone Oral Suspension Up to 48 Weeks in Patients With Amyotrophic Lateral Sclerosis (Study MT-1186-A02)

Jeffrey Rothstein et al. Muscle Nerve. 2025 Sep.

Abstract

Introduction/aims: An On/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is approved in the US for the treatment of amyotrophic lateral sclerosis (ALS). Placebo-controlled clinical trials showed IV edaravone slows the rate of physical functional decline. This study evaluated whether investigational daily dosing displayed superior efficacy vs. approved on/off dosing of edaravone oral suspension, and assessed safety and tolerability, over 48 weeks in patients with ALS.

Methods: Study MT-1186-A02 (NCT04569084) was a multicenter, phase 3b, double-blind, parallel group, superiority study that randomized patients to edaravone oral suspension (105-mg dose) administered Once Daily or the same edaravone oral suspension dose administered according to the approved On/Off regimen including placebo to mimic daily drug dosing. Patients had definite or probable ALS, baseline forced vital capacity ≥ 70%, and baseline disease duration ≤ 2 years. The primary endpoint was a combined assessment of function and survival (CAFS) at week 48, which included change in ALS Functional Rating Scale-Revised (ALSFRS-R) and time to death.

Results: CAFS at week 48 indicated Once Daily dosing did not show a statistically significant difference vs. approved on/off dosing (p = 0.777). Both dosing regimens provided comparable change from baseline ALSFRS-R total score to week 48 (least squares mean difference: 0.27 [95% CI -1.43 to 1.97]). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.

Discussion: Daily edaravone oral suspension did not show superiority and had equivalent safety and tolerability vs. the approved On/Off regimen, reinforcing the appropriateness of the approved dosing regimen.

Keywords: amyotrophic lateral sclerosis; clinical trial; edaravone; efficacy; safety.

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Conflict of interest statement

J.R. is a consultant for Expansion Therapeutics, National Institutes of Health, Department of Defense, F Prime, The ALS Association; A.G. has served as a consultant for Mitsubishi Tanabe Pharma Inc.; S.D. and M.C. have nothing to disclose; L.Z. has received honoraria for consulting with MTP, Biogen, Amylyx, and Cytokinetics; A.C. serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Denali Pharma, A.C. Immune, Biogen, Lilly, and Cytokinetics and has received a research grant from Biogen; G.S., H.Y., and M.A. have served as medical advisors for Mitsubishi Tanabe Pharma Corporation; M.D. is a medical advisor for the MT‐1186‐A02 study; V.T. is an employee of Mitsubishi Tanabe Pharma Europe Ltd.; N.S. has served as a statistical consultant for NeuroDerm and Mitsubishi Tanabe Pharma Inc.; D.S., F.T., A.S., A.W., M.H., and S.A. are employees of Mitsubishi Tanabe Pharma America Inc.

Figures

FIGURE 1
FIGURE 1
Patient disposition. DBT, double‐blind treatment; PK, pharmacokinetic. aOne patient randomized to the On/Off treatment group was excluded from the FAS and SAF because the patient did not receive any study treatment. bPatients who enrolled into the extension study, MT‐1186‐A04, were not required to complete the 2‐week safety follow‐up visit.
FIGURE 2
FIGURE 2
Effect of edaravone oral suspension across regions in Study MT‐1186‐A02 based on change in ALSFRS‐R total score at Week 48. ALSFRS‐R, Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised; BL, baseline; LS, least squares; SD, standard deviation; SE, standard error.
FIGURE 3
FIGURE 3
(Post hoc) Effect of edaravone across studies based on change in ALSFRS‐R total score at week 48 [4]. ALSFRS‐R, Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised; BL, baseline; LS, least squares; SD, standard deviation; SE, standard error; Study 19, Study MCI186‐19; Study A02, Study MT‐1186‐A02. Studies MCI186‐19 and MT‐1186‐A02 had different study designs. Some of these differences included different study populations and statistical analysis methods [4].
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