Oral Edaravone – Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis

ABSTRACT

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications.

Areas covered

The authors performed a review of the published literature using the United States (US) National Library of Medicine’s PubMed.gov resource to describe the pharmacokinetics, pharmacodynamics, safety, and efficacy of oral edaravone, as well as pertinent completed and ongoing clinical trials, including the oral edaravone clinical trial development program. The clinical profile of oral edaravone is also discussed.

Expert opinion

Edaravone has been shown to slow the rate of motor function deterioration experienced by patients with ALS. As the oral formulation has been approved, patients with ALS may use it alone or in combination with other approved therapeutics. Additional clinical trials and real-world evidence are ongoing to gain further understanding of the clinical profile of oral edaravone.

KEYWORDS:

• Amyotrophic lateral sclerosis
• clinical trials
• edaravone
• neuromuscular degeneration
• oral formulation
• safety

Article highlights

• While the exact mechanism of action remains unknown, edaravone acts as a free radical scavenger that has demonstrated reduction of oxidative stress, which is believed to be associated with the pathology of ALS

• Edaravone is a US FDA-approved drug shown in clinical trials to slow the rate of physical functional decline in patients with ALS, and is one of only four FDA-approved active pharmaceutical agents for ALS

• Study 19 (MCI186-19) was a randomized, double-blind, parallel-group, placebo-controlled phase 3 trial designed to establish the safety and efficacy of IV edaravone for the treatment of ALS

• Oral edaravone was FDA approved in May 2022 based on the 24-week results of a global phase 3 study evaluating its safety and tolerability (Study A01; MT-1186-A01) and a clinical pharmacology study that compared the pharmacokinetics of IV and oral edaravone (Study J03; MT-1186-J03)

• Oral edaravone can be administered orally or through a nasogastric/percutaneous endoscopic gastrostomy tube

• Additional clinical studies and real-world evidence will be helpful in gaining an improved understanding of the benefits of oral edaravone alone and in combination with other approved ALS therapeutics

Acknowledgments

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

Declaration of interest

GL Pattee and A Genge have served as consultants for Mitsubishi Tanabe Pharma, Inc. P Couratier has served as a consultant for Biogen and as an editor for Elsevier. C Lunetta has served as a scientific consultant for Mitsubishi Tanabe Pharma Europe, Cytokinetics, Neuraltus, and Italfarmaco. G Sobue, M Aoki and H Yoshino have served as medical advisors for Mitsubishi Tanabe Pharma Corporation. C Jackson serves on the Data and Safety Monitoring Board for Mitsubishi Tanabe Pharma America, Inc., and Anelixis. J Wymer has received research funding from Mitsubishi Tanabe Pharma America, Inc. A Salah is an employee of Mitsubishi Tanabe Pharma America, Inc., and S Nelson is a former employee of Mitsubishi Tanabe Pharma America, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was funded by Mitsubishi Tanabe Pharma America, Inc.