Phase 3b Study MT-1186-A02 to Investigate the Superiority of Daily vs FDA-approved On/Off Oral Edaravone (Radicava ORS®) Dosing in Patients with ALS

Topic:

Clinical Trials

Poster Number: P271

Author(s):

Jeffrey Rothstein, MD, PhD, Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Angela Genge, MD, Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, Shari De Silva, MD, Woodland Research Northwest, Rogers, Arkansas, USA, Lorne Zinman, MD, MSc, FRCP(C), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, Marvin Chum, MD, MSc, FRCP(C), McMaster University Health Sciences Centre, Hamilton, ON, Canada, Adriano Chio, MD, FAAN, Università degli Studi di Torino, Centro Regionale Esperto per la Sclerosi Laterale Amiotrofica, Gen Sobue, MD, PhD, Nagoya University Graduate School of Medicine, Nagoya; Aichi Medical University, Aichi, Japan, Manabu Doyu, MD, PhD, Department of Neurology, Aichi Medical University, Nagakute, Aichi, Japan, Daniel Selness, RN, BA, MBA, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Vesna Todorovic, MD, MPhil, Mitsubishi Tanabe Pharma Europe, Ltd, London, United Kingdom, Nissim Sasson, MA, NStat Solutions, Biostatistical Services, Rehovot, Israel, Fumihiro Takahashi, PhD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Alejandro Salah, MD, PhD, MBA, MHA, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Art Wamil, MD, PhD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Stephen Apple, MD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA

BACKGROUND: An on/off dosing regimen of Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [MTPA]) and Radicava ORS® (edaravone) oral suspension (MTPA, hereafter “MTPA oral edaravone”) was approved by the US Food and Drug Administration (FDA) for the treatment of amyotrophic lateral sclerosis (ALS) in 2017 and 2022, respectively. Clinical trials showed that MTPA edaravone slows the rate of physical functional decline.

OBJECTIVE: To evaluate whether investigational daily dosing displayed superior efficacy vs the approved on/off dosing regimen of MTPA oral edaravone in patients with ALS based on combined assessment of function and survival (CAFS), including change in ALS Functional Rating Scale-Revised (ALSFRS-R) score and time to death, as well as assess safety and tolerability, over 48 weeks.

RESULTS: Study MT-1186-A02 (NCT04569084) was a multi-center, phase 3b, double-blind, parallel group superiority study that randomized patients to MTPA oral edaravone (105-mg dose) administered once daily or the same MTPA oral edaravone dose administered according to the FDA-approved on/off regimen. Patients had definite or probable ALS, baseline forced vital capacity ≥70%, and baseline disease duration ≤2 years. At week 48, CAFS, including change in ALSFRS-R score and time to death, indicated daily dosing did not show a statistically significant difference vs FDA-approved on/off dosing. MTPA oral edaravone was well tolerated and no new safety concerns were identified in either group in Study MT-1186-A02.

CONCLUSIONS: MTPA oral edaravone daily dosing did not show superiority to the FDA-approved on/off regimen in the CAFS, and was comparable in safety, efficacy, and tolerability to the on/off dosing regimen, therefore reinforcing the appropriateness of the FDA-approved regimen.

Sponsorship: Sponsored by Mitsubishi Tanabe Pharma America, Inc.

Acknowledgements: The authors thank Irene Brody, VMD, PhD of p-value communications, Cedar Knolls, NJ, USA, for providing medical writing support. Editorial support was also provided by p-value Communications. This support was funded by Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, USA, in accordance with Good Publication Practice Guidelines 2022.