Mitsubishi Tanabe Pharma America has announced the publication of a retrospective analysis in Muscle and Nerve that provides new evidence supporting the long-term benefits of RADICAVA ORS (edaravone) in patients with amyotrophic lateral sclerosis (ALS). The analysis compared patients taking the oral suspension formulation with historical placebo controls from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, revealing significant improvements in both survival outcomes and functional preservation.
Significant Survival Benefits Observed
The primary analysis evaluated 78 propensity score-matched patients treated with RADICAVA ORS compared to 78 matched historical placebo controls. The results demonstrated a substantial survival advantage for patients receiving the oral edaravone formulation. Over approximately 22 months, only 3 out of 78 patients (3.8%) died in the RADICAVA ORS group compared to 14 out of 78 patients (17.9%) in the PRO-ACT placebo group (P=0.005).
The baseline risk-adjusted hazard ratio showed an 84% decreased risk of death for patients in the combined RADICAVA ORS group versus the PRO-ACT placebo group (P=0.005). This finding suggests a significantly longer survival time for patients receiving the treatment.
In the broader post-hoc analysis involving 210 patients from studies MT-1186-A01/A02/A03/A04, the survival benefit was even more pronounced. A covariate-adjusted restricted mean survival time analysis over approximately 34 months showed a mean prolongation of 7.3 months in survival, with RADICAVA ORS patients surviving an average of 29.6 months compared to 22.2 months for PRO-ACT placebo patients (P<0.001).
Functional Decline Significantly Slowed
The analysis also demonstrated that RADICAVA ORS treatment was associated with slower rates of functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). In the primary analysis cohort, both groups had a mean baseline ALSFRS-R score of 41.0 points. Over 48 weeks, the least squares mean change from baseline was -8.4 ± 1.0 points for RADICAVA ORS patients compared to -14.1 ± 1.0 points for PRO-ACT placebo patients, representing a clinically meaningful difference of 5.6 points (95% CI, 2.8-8.4; P<0.001).
The broader post-hoc cohort confirmed these findings, showing a difference of 2.4 points between groups (95% CI, 0.6-4.2; P=0.008), with RADICAVA ORS patients experiencing a mean change of -10.5 ± 0.7 points compared to -12.9 ± 0.6 points for placebo patients.
Clinical Context and Real-World Impact
"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, M.D., Vice President of Medical Affairs at MTPA. "By publishing this analysis, we aim to deliver meaningful insights for healthcare providers, patients and caregivers."
Since its launch three years ago, RADICAVA ORS has been used to treat over 13,519 people living with ALS in the United States. More than 1,378 U.S. healthcare providers have prescribed the medication, and 82% of patients who started treatment between June 2022 and March 2024 continued therapy for three months or more.
Study Methodology and Limitations
The analysis utilized propensity score matching on 10 baseline variables to assess the impact of RADICAVA ORS on function and survival. The PRO-ACT database, which serves as the world's largest ALS clinical trial data repository, provided historical placebo control data from 36 phase II/III clinical trials involving over 12,500 fully anonymized longitudinal patient records.
Lead author Fumihiro Takahashi, Senior Biostatistician at Mitsubishi Tanabe Pharma Corporation, noted the importance of these findings: "There remains no cure for ALS, underscoring the importance of treatments that can slow functional loss for those living with this fatal neurodegenerative condition. This analysis provides additional data to help characterize functional outcomes and potential impact of RADICAVA ORS on disease progression in ALS."
The researchers acknowledge several important limitations. The results are not generalizable and cannot be used to determine definitive conclusions about treatment effects. The p-values are nominal as no multiplicity adjustments were made, and this was a non-randomized analysis that should be interpreted with caution.
Treatment Profile and Administration
RADICAVA ORS was approved by the FDA in May 2022 and received Orphan Drug Exclusivity in 2024 based on its major contribution to patient care by providing an oral suspension route that avoids the burdens of intravenous administration. The medication follows a specific dosing regimen: daily dosing for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle, with subsequent cycles involving daily dosing for 10 out of 14 days followed by a 14-day drug-free period.
The most common adverse events reported in previous clinical trials include contusion (15%), gait disturbance (13%), and headache (10%). In the pivotal open-label safety trial for RADICAVA ORS, the most frequently reported adverse events at 24 weeks were muscular weakness (16.2%), fall (15.7%), and fatigue (7.6%).
