Extension Study MT-1186-A04 Evaluating Oral Edaravone (Radicava ORS®) Continued Efficacy and Safety up to an Additional 48 Weeks in Patients With ALS

Topic:

Clinical Trials

Poster Number: P282

Author(s):

Angela Genge, MD, Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, Jeffrey Rothstein, MD, PhD, Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, 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, Michelle Cecić, BA, 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: 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 US Food and Drug Administration (FDA)-approved for amyotrophic lateral sclerosis (ALS) treatment in 2017 and 2022, respectively. Clinical trials showed that MTPA edaravone slows physical functional decline in patients with ALS.

OBJECTIVE: Continue to examine the efficacy and safety of the investigational once daily and FDA-approved on/off MTPA oral edaravone dosing regimens in patients with ALS for up to an additional 48 weeks in extension Study MT-1186-A04.

METHODS: Study MT-1186-A04 (NCT05151471) was a phase 3b, multi-center, randomized, double-blind, parallel group extension study for up to an additional 48 weeks following the initial 48 weeks of Study MT-1186-A02, where patients had been randomized to an investigational once daily or FDA-approved on/off dose of MTPA oral edaravone (105-mg dose). Patients who met Study MT-1186-A04 eligibility criteria, including successful Study MT-1186-A02 visit completion, continued in the same treatment regimen they were on during Study MT-1186-A02. The primary efficacy endpoint for MT-1186-A04 was time from randomization in Study MT-1186-A02 to ≥12-point decrease in ALS Functional Rating Scale-Revised (ALSFRS-R) or death, whichever happened first.

RESULTS: Over 96 weeks including the Study MT-1186-A02 treatment period, results for the primary endpoint 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-A04.

CONCLUSIONS: Similar to the results obtained in MT-1186-A02, in MT-1186-A04, daily MTPA oral edaravone did not show superiority to the FDA-approved on/off regimen (same safety, efficacy and tolerability profile) from the time of the randomization date in Study MT-1186-A02 ≥12-point decrease in ALSFRS-R or death, whichever happened first, and reinforces the appropriateness of the FDA-approved regimen.