Post Hoc Data Suggest Edaravone Helpful in Bulbar-Onset ALS

By Megan Brooks

March 31, 2020

NEW YORK (Reuters Health) - For patients with bulbar-onset amyotrophic lateral sclerosis (ALS), initiating treatment with edaravone appears to provide a benefit in terms of physical functioning regardless of baseline lung function, according to a post hoc analysis of data from a phase-3 trial.

The results, scheduled for presentation at the 2020 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, were presented in a virtual session March 24 by Dr. Gary Pattee with Neurology Associates of Lincoln, Nebraska.

Edaravone (Radicava), from Mitsubishi Tanabe Pharma America (MTPA), was approved in the United States in 2017 to slow loss of physical function in patients with ALS.

Study 19 was a manufacturer-sponsored, phase-3, randomized, double-blind, placebo-controlled trial of 137 patients with ALS treated with edaravone or placebo for 48 weeks; 107 had limb-onset ALS and 30 had bulbar-onset ALS.

In the full Study 19 population, ALS patients had significantly less functional decline with edaravone than placebo.

The post hoc analysis of Study 19 compared the efficacy of edaravone in patients with bulbar-onset and limb-onset disease, and separately in bulbar-onset patients with forced vital capacity (FVC) of 80% or greater (n=5) versus less than 80% (n=21).

The results showed that patients with bulbar- and limb-onset disease both experienced a slower reduction in physical function, as measured by the Revised ALS Functional Rating Score (ALSFRS-R), with edaravone versus placebo through 48 weeks, Dr. Pattee reported.

In addition, after switching to edaravone, participants with either bulbar- or limb-onset ALS experienced a reduction in ALSFRS-R score loss from baseline through 48 weeks, and there was a "notable change" in slope in ALSFRS-R score decline, Dr. Pattee said.

Edaravone appeared to slow disease progression in bulbar-onset patients with FVC at or above 80% as well as those with FVC below 80%. The differences were not statistically significant, likely due to the small number of patients in the analyses, Dr. Pattee noted.

"As a post hoc, subgroup analysis of Study 19, this study is subject to the limitations inherent in post-hoc analyses, i.e., the analyses were not prespecified in Study 19, there were smaller sample sizes in each subgroup, and there is a lack of control for type 1 error," Dr. Pattee cautioned in his presentation.

In a phone interview with Reuters Health, Dr. Matthew Harms of the ALS Center at Columbia University in New York City, who wasn't involved in the analysis, said it's "intriguing" to see that bulbar-onset patients "seemed to have a similar benefit to the limb-onset patients, but with the caveat that the numbers were very small."

He also said there seems to be a subgroup of patients who might actually get worse when put on edaravone. "There is lots of back and forth on patient websites and chat rooms with some patients saying they got worse. My personal experience is that about a third of the people that I put on it, did seem or felt like they were getting worse. Clearly, this is all anecdotal," said Dr. Harms, an associate professor of neurology.

"What we don't know is whether it's the drug or whether it's a stressor on the body of having to go into the hospital for a catheter to be placed and the stress of the infusion and the procedure," he said.

Currently, edaravone is administered intravenously. The first treatment cycle consists of daily doses for 14 days, followed by 14 days with no treatment. In subsequent cycles, a patient receives 10 doses over 14 days and then foregoes the drug over the next 14 days.

This post hoc analysis is "important in that it's an attempt to go back and do subgroup analyses, trying to identify who is likely to benefit the most and who may be is at higher risk for deterioration," Dr. Harms told Reuters Health.

Dr. Harms also said the manufacturer has taken "an important next step" in what amounts to an elaborate post-marketing surveillance study called REFINE-ALS (

"The goal is to identify subgroups who may do better or who may do worse on the drug," said Dr. Harms, who is a collaborator on the study. The company is also testing an oral version of the drug.

The study was funded and conducted by Mitsubishi Tanabe Pharma America. Three authors are employees of the company.

SOURCE: Muscular Dystrophy Association Clinical and Scientific Conference, presented March 24, 2020.