Radicava ORS slows ALS disease progression, improves survival
Results were compared against historical controls from previous clinical trials
Treatment with Radicava ORS (edaravone) significantly slowed declines in physical function and improved survival outcomes for people with amyotrophic lateral sclerosis (ALS) compared with historical controls from the PRO-ACT database who’d received a placebo in previous clinical trials.
The findings were presented by Mitsubishi Tanabe Pharma America (MTPA), which markets Radicava ORS in the U.S., at the 2024 annual meeting of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS).
“Results from analyses of the long-term function and survival of Radicava ORS versus propensity score-matched Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) historical controls in people with ALS suggest Radicava ORS increased survival outcomes and decreased physical function decline versus controls,” Gustavo A. Suarez Zambrano, MD, MTPA’s vice president of medical affairs, said in a statement to ALS News Today.
Radicava ORS is an oral version of the infusion therapy Radicava, which in 2017 became the first new ALS treatment to win approval in the U.S. in more than two decades. The medication is thought to work by lowering oxidative stress, a type of cellular damage that contributes to nerve degeneration in ALS.
Both Radicava and Radicava ORS are administered in a monthly on/off dosing schedule where patients first receive daily treatment for 14 consecutive days, followed by a two-week period without dosing. In subsequent cycles, patients receive treatment for 10 days, then don’t take it for the next 18 days.
Testing once-daily dosing of Radicava ORS
Because this regimen can be sometimes difficult to follow, MTPA sponsored a Phase 3b clinical trial, dubbed MT-1186-A02 (NCT04569084) that tested the approved dosing schedule against once-daily dosing, with no off-treatment periods, for 48 weeks, or nearly a year. Of the 384 patients included in the original study, 202 entered an extension trial called MT-1186-A04 (NCT05151471) that continued testing these two dosing regimens against each other for 48 more weeks.
Results from the Phase 3 trial and its extension were presented in a poster titled, “Phase 3b Extension Study MT-1186-A04 to Evaluate the Continued Efficacy and Safety of Radicava ORS (Oral Edaravone) for Up to an Additional 48 Weeks in Patients With Amyotrophic Lateral Sclerosis.”
There were no differences overall in disease progression rates or survival outcomes in patients given the daily treatment compared with those who received the on/off schedule. The findings showed that 25% of patients given daily Radicava ORS had side effects related to the treatment compared with 16.8% of those given the on/off regimen. Serious side effects related to treatment, trouble swallowing being the most frequent, were also more common with once-daily dosing.
The results showed “the on/off regimen of Radicava ORS is the most appropriate regimen for patients with ALS,” according to a press release from MTPA.
Studies support efficacy of Radicava ORS
In a second poster at NEALS, researchers shared data from an analysis that compared outcomes from patients in these and other Radicava ORS trials, namely the MT-1186-A01 Phase 3 trial (NCT04165824) and its MT-1186-A03 extension study (NCT04577404) that supported the approval of Radicava ORS, against data from a historical database called PRO-ACT.
PRO-ACT is a large database that holds information from more than 12,000 ALS patients who participated in previous Phase 2/3 clinical trials. Patients in the Radicava ORS trials were matched with placebo-treated patients in PRO-ACT who had similar characteristics, including sex, age, and body weight, as well as disease duration, severity, and rate of progression before treatment.
In the poster, “Analysis of Long-term Function and Survival of Radicava ORS (Oral Edaravone)-Treated Patients With Amyotrophic Lateral Sclerosis vs Propensity Score-Matched PRO-ACT Historical Controls,” researchers used statistical models to compare survival rates in the placebo and Radicava ORS groups.
They saw that survival was significantly better among those given Radicava ORS in the on/off trials, who lived about two more years than the PRO-ACT controls. The medication, given either as an on-off or daily schedule, reduced the likelihood of death by about 84%.
Additional analyses that included data from all four trials also showed a survival benefit: throughout nearly three years of follow-up (35 months), less than 1 in 7 (13.8%) of the patients given Radicava ORS died compared with nearly 32.9% of those in the control group. This means patients given Radicava ORS in these trials lived about 7.3 months longer and had a 66% lower risk of death than the placebo-treated patients from PRO-ACT.
In both analyses, changes in the ALS Functional Rating Scale Revised (ALSFRS-R) after about 48 weeks likewise showed a significantly slower decline in the ability to perform everyday tasks among the Radicava ORS group than the controls. The analyses “provide evidence for a slowing of functional decline and improved survival outcomes with long-term [Radicava ORS] treatment versus PRO-ACT placebo group patients with ALS,” the researchers said.
“These findings, along with final results from Study MT-1186-04, which support the continued use of the FDA-approved on/off regimen of Radicava ORS, further reinforce MTPA’s commitment to addressing unmet needs, advancing research, and driving scientific innovation in ALS,” Suarez Zambrano said.
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