Radicava ORS fares well in Phase 3 clinical trial

Study tracked the oral form of Radicava for nearly a year

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Note: This story was updated March 10, 2023, to correct a secondary headline to note the therapy was tracked for less than a year. The story also clarifies the timing of results from a Phase 3 clinical trial and that edaravone is believed to reduce oxidative stress.

Radicava ORS, an oral formulation of Radicava (edaravone), was well tolerated among people with amyotrophic lateral sclerosis (ALS) over nearly a year of treatment in a clinical trial.

Findings from the trial had been announced previously by the therapy’s developer Mitsubishi Tanabe Pharma America (MTPA), and 24-week data from the trial helped form the basis of the U.S. Food and Drug Administration (FDA)’s approval of Radicava ORS last year.

The results have now undergone peer review and were detailed in the study, “Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48 weeks of treatment,” published in Muscle & Nerve. The work was funded by MTPA.

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“We’re encouraged by the data that we continue to collect from the global Phase 3 trial of Radicava ORS, demonstrating a favorable safety profile after 48 weeks of treatment,” Gustavo Suarez Zambrano, MD, vice resident of medical affairs at MTPA, said in a press release. “These data build upon the study’s 24-week findings that supported the FDA approval of Radicava ORS.”

While the mechanism of action of edaravone, the active agent in Radicava and Radicava ORS, is unknown, it is believed to reduce oxidative stress — a type of cell damage that’s thought to play a critical role in driving nerve cell death in ALS. The original therapy was designed to be delivered intravenously (via infusion into the bloodstream), and results from clinical trials showed that it slowed functional decline in people with early ALS.

Radicava ORS was designed to deliver the same active ingredient, but in an oral form that would be more convenient for patients. Pharmacological studies have demonstrated that a 105 mg dose of oral Radicava ORS delivers the same amount of edaravone as the approved 60 mg dose of intravenous Radicava. MTPA conducted a Phase 3 clinical trial (NCT04165824) aiming to assess the safety of the oral formulation.

The study enrolled 185 adults diagnosed with ALS at sites in the U.S., Canada, Japan, Germany, France, and Italy. The average participant age was around 60 years, and the average disease duration was about 1.5 years. About 80% of patients had limb-onset disease, while the rest had bulbar-onset.

Four-week cycles

All of the patients were treated with Radicava ORS, administered in four-week treatment cycles similar to how the intravenous formulation is given: two weeks of taking the therapy, and then two weeks off in the first cycle, and then 10 days of treatment in the first two weeks, followed by two weeks off in subsequent cycles.

Most of the patients (87%) also were being treated with riluzole (sold as Rilutek and other formulations), and nearly one in five (18.4%) had been on intravenous Radicava previously.

The study lasted 48 weeks (almost a year). About 25% of the participants did not complete the full 48 weeks of treatment, mainly due to experiencing safety issues, death due to ALS, or due to the patient’s choice. The researchers said this rate is “comparable with or slightly lower than other recent clinical trials in ALS.”

Safety-related events were reported in nearly every participant over the course of the study, though many of these events were judged to be a result of ALS disease progression and not considered related to treatment with Radicava ORS.

By 48 weeks, about one quarter (24.9%) of the participants had experienced safety-related events that were judged by study investigators to be likely side effects of the oral therapy. The most common side effects were fatigue, dizziness, headache, and constipation. No treatment-related side effects were judged to be serious.

Findings consistent with IV Radicava

These findings were generally consistent with the known safety profile of intravenous Radicava, the researchers said.

“The 48-week results from this trial suggest that RADICAVA ORS was well tolerated, and support its long-term use as a treatment for ALS. Our hope is for these data to provide additional information to physicians who are considering this oral treatment option for their patients,” said Gary Pattee, MD, a neurologist and ALS specialist who works in Nebraska.

Over the course of the study, the average forced vital capacity (FVC) — a standardized measure of lung function based on how much someone can forcibly exhale — decreased by an average of 25.1%. Again, the researchers said this is consistent with prior trial results for intravenous Radicava, where the average decline in FVC was 15.6% for those on therapy, compared to 20.4% for patients given a placebo.

“This trial provides safety data to support the use of oral [Radicava ORS], which expands on existing evidence supporting the use of FDA-approved [intravenous Radicava] and the recently approved oral suspension formulation,” the scientists concluded.