New analysis shows Radicava ORS slows ALS decline
Data from trials, extensions confirm treatment benefits
A retrospective analysis using data from two clinical studies and their extension periods showed that Radicava ORS, an oral formulation of edaravone, slows functional decline and helps adults with amyotrophic lateral sclerosis (ALS) live longer.
“This analysis provides additional data to help characterize functional outcomes and potential impact of Radicava ORS on disease progression in ALS,” Fumihiro Takahashi, PhD, the study’s first author and senior biostatistician at Mitsubishi Tanabe Pharma, the drug’s developer, said in a company press release.
The study, “Analysis of Long-term Function and Survival of Edaravone Oral Suspension-Treated Patients With Amyotrophic Lateral Sclerosis Using PRO-ACT Data as Historical Placebo Controls,” was published in Muscle & Nerve. It was funded by Mitsubishi Tanabe Pharma America (MTPA), which markets Radicava ORS in the U.S.
“These findings contribute to the ongoing effort to address unmet needs in ALS treatment by providing insight into the benefits observed with Radicava ORS,” said Gustavo A. Suarez Zambrano, MD, vice president of medical affairs at MTPA. “By publishing this analysis, we aim to deliver meaningful insights for healthcare providers, patients and caregivers.”
ALS occurs due to the loss of motor neurons, which control voluntary movements. The causes of the disease are not fully understood. Still, one central mechanism implicated in motor neuron death is oxidative stress, or an imbalance between the production of toxic oxygen-containing molecules and the body’s ability to neutralize them. While this can affect all cells, nerve cells are particularly sensitive to oxidative stress.
Long-term benefits confirmed using database
Radicava ORS and Radicava, a formulation for intravenous (into-the-vein) infusion, both contain the active ingredient edaravone, which works by scavenging oxygen-containing molecules and preventing them from damaging motor neurons.
Radicava ORS approval was supported in part by data from a global Phase 3 trial called MT-1186-A01 (NCT04165824) and its long-term extension study MT-1186-A03 (NCT04577404). A total of 185 participants were enrolled, and all received Radicava ORS for 48 weeks, or nearly one year, after which they could enter the extension and receive the medication for up to 96 more weeks.
A Phase 3b clinical trial, MT-1186-A02 (NCT04569084), was conducted as part of a post-approval commitment with the U.S. Food and Drug Administration to test the approved 10-day-on, 18-day-off regimen against once-daily dosing for 48 weeks. An extension study called MT-1186-A04 (NCT05151471) followed, allowing participants to receive treatment for up to another 48 weeks. No differences were observed between the two dosing schedules in either study.
Because no studies have compared Radicava ORS with a placebo in the long term, researchers set out to compare outcomes from patients in the two trials with those of placebo-treated patients in the PRO-ACT database, which contains clinical and demographic data from thousands of ALS patients who took part in previous clinical trials.
The team first compared 78 patients treated with Radicava ORS in the MT-1186-A02/A04 trials with 78 matched historical placebo controls from PRO-ACT. Control patients had not received the active treatment in their respective trials but could have received riluzole, which was also allowed in the Radicava ORS trials.
After about 22 months, or nearly two years, three (3.8%) patients treated with Radicava ORS — either under the approved on/off dosing or once daily — had died, compared with 14 (17.9%) of the historical controls. This translated into an 84% lower risk of death in the Radicava ORS group.
A broader analysis then compared patients from all four Radicava ORS studies — MT-1186-A01/A02/A03/A04 — with the PRO-ACT placebo controls. A total of 210 Radicava ORS-treated patients and 210 matched controls were included.
Over about 35 months, or nearly three years, fewer patients died with Radicava ORS (13.8% vs. 32.9%). This translated into a 66% lower risk of death and a 7.3-month extension in survival time.
Functional ability, as measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), was also better preserved with Radicava ORS compared with the historical placebo. In the main analysis, patients began with an average ALSFRS-R score of 41 points, and after 48 weeks, the change in ALSFRS-R score was smaller with Radicava ORS than with a placebo (8.4 points vs. 14.1 points). This 5.6-point difference suggested slower functional decline with treatment.
In the larger, post-hoc analysis, this difference was 2.4 points.
“These results provide evidence for a slowing of functional decline and improved survival,” the researchers wrote. While the analysis was not based on randomized studies and no adjustments were made for testing multiple comparisons, its results “are consistent with and provide additional supporting evidence to previously published studies,” they said.
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