Results from this analysis were published in Muscle and Nerve
JERSEY CITY, N.J., Aug. 19, 2025 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the publication of a retrospective analysis of patients living with amyotrophic lateral sclerosis (ALS) in Muscle and Nerve. The analysis evaluated patients taking RADICAVA ORS® (edaravone) compared with Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) historical placebo controls (patients who did not receive active investigational treatment, but may have received riluzole in their respective clinical trials), with evidence suggesting treatment with RADICAVA ORS decreased physical functional decline and offering insights into survival outcomes.
"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."
The primary analysis, based on data from clinical studies MT-1186-A02/A04, evaluated long-term survival and functional outcomes of 78 propensity score-matched patients treated with RADICAVA ORS compared to 78 matched historical placebo controls from the PRO-ACT database.
The main statistical comparison was made between the Combined (FDA approved On/Off + investigational Once Daily) RADICAVA ORS versus PRO-ACT placebo group. The post-hoc analysis, based on data from clinical studies MT-1186-A01/A02/A03/A04, expanded the evaluation to a broader ALS population (n=210 RADICAVA ORS patients vs. 210 PRO-ACT placebo patients) to confirm robustness of the initial results.
Propensity score matching on 10 baseline variables was used to assess the impact of RADICAVA ORS suspension on function and survival. The analysis showed 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 analysis also showed a smaller ALS Functional Rating Scale-Revised (ALSFRS-R) change from baseline, demonstrating a slower rate of functional decline observed over 48 weeks.
Key findings from the analysis include:
- An association was observed between treatment with RADICAVA ORS and improved survival outcomes compared to matched historical placebo patients in the PRO-ACT database.
- In the primary analysis cohort, the combined RADICAVA ORS group demonstrated a survival benefit vs the PRO-ACT placebo group over approximately 22 months (P=0.005). Three out of the 78 patients (3.8%) died in the RADICAVA ORS group vs 14/78 (17.9%) in the PRO-ACT placebo group. The baseline risk-adjusted hazard ratio showed an 84% decreased risk of death, indicating a longer survival time, in the combined RADICAVA ORS vs PRO-ACT placebo groups (P=0.005). Additionally, positive trends favoring both the Once Daily (n=65) and On/Off RADICAVA ORS (n=65) groups vs PRO-ACT placebo group (n=65) were observed for number of deaths and time to death, but neither one reached statistical significance.
- In the post hoc broader ALS cohort, patients from studies MT-1186-A01/A02/A03/A04 showed a difference in time to death over approximately 35 months (P<0.001) Additionally, a post hoc covariate-adjusted restricted mean survival time (RMST) analysis to confirm the average survival time over approximately 34 months showed a mean prolongation of 7.3 months in survival (On/Off and Once Daily RADICAVA ORS: 29.6 months; PRO-ACT placebo group: 22.2 months; P<0.001). The proportion of events in the RADICAVA ORS suspension group (29/210 patients, 13.8%) was significantly smaller than the PRO-ACT placebo group (69/210 patients, 32.9%). RMST is a metric that estimates the average time a group survives relative to a comparator.
- Over 48 weeks, treatment with RADICAVA ORS was associated with a slower rate of decline in ALSFRS-R scores, suggesting potential benefit in maintaining physical function compared to matched PRO-ACT placebo group. In the primary analysis cohort, patients in both groups had a mean baseline ALSFRS-R score of 41.0 points. The least squares (LS) mean change from baseline to week 48 was −8.4 ± 1.0 points for RADICAVA ORS compared to −14.1 ± 1.0 points for PRO-ACT placebo patients, a difference of 5.6 points (95% CI, 2.8–8.4; P<0.001). In the broader post-hoc cohort, the LS mean change was −10.5 ± 0.7 points for RADICAVA ORS compared to −12.9 ± 0.6 points for PRO-ACT placebo patients, a difference of 2.4 points (95% CI, 0.6–4.2; P=0.008).
- Lastly, it is important to note that results from this analysis are not generalizable and cannot be used to determine definitive conclusions about the effects of treatment. The p-values are nominal as no multiplicity adjustments were made for these analyzed data. Additionally, this was a non-randomized analysis, and results should be interpreted with caution. Please see publication for additional limitations.
"There remains no cure for ALS, underscoring the importance of treatments that can slow functional loss for those living with this fatal neurodegenerative condition," said Fumihiro Takahashi, Senior Biostatistician, Mitsubishi Tanabe Pharma Corporation and lead author of the publication. "This analysis provides additional data to help characterize functional outcomes and potential impact of RADICAVA ORS on disease progression in ALS."
This analysis was funded and conducted by MTPA. The full publication is titled, "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."
About the PRO-ACT Database
PRO-ACT Dataset is the world's largest ALS clinical trial data repository, compiling placebo and treatment-arm data from 36 phase II/III clinical trials and over 12,500 fully anonymized longitudinal Subject records funded by The ALS Therapy Alliance, Prize4Life, Inc., Northeast ALS Consortium (NEALS), Neurological Clinical Research Institute of Mass. General Hospital, ALS Finding A Cure, and The ALS Association. Neurological Clinical Research Institute of Mass. General Hospital created and maintained the PRO-ACT Dataset and serves as the coordinating center and data distributor of the PRO-ACT Dataset. Find out more at www.alsdata.org.
About Studies MT-1186-A01/A02/A03/A04
Study MT-1186-A01 (NCT04165824) was a phase 3, global, multicenter, open-label study that evaluated the long-term safety and tolerability of the approved edaravone oral suspension 105 mg On/Off dosing regimen over 48 weeks, and Study MT-1186-A03 (NCT04577404) was its extension study, which provided up to 96 weeks of additional treatment. Study MT-1186-A02 (NCT04569084), a post-marketing commitment following the FDA approval of RADICAVA® (edaravone), was a phase 3b, multicenter, double-blind, parallel-group, randomized study that evaluated whether investigational Once Daily edaravone oral suspension dosing was superior to the approved On/Off dosing based on Combined Assessment of Function and Survival, and assessed safety and tolerability over 48 weeks in patients with ALS; and Study MT-1186-A04 (NCT05151471) was its extension study, which provided up to 48 weeks of additional treatment.
In Study MT-1186-A02, a pre-planned futility analysis was conducted after 50% of the planned study population (N=190) reached 48 weeks, which assessed the study's primary endpoint and the probability of the study results changing if all participants completed the 48-week study period. Through that interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that there was a low statistical probability for the investigational once-daily dosing regimen to show superiority to the current on/off dosing regimen as measured by the ALS Functional Rating Scale Revised (ALSFRS-R) score at study completion; therefore, study discontinuation was recommended by the IDMC.
About RADICAVA ORS® (edaravone)
The U.S. Food and Drug Administration (FDA) approved RADICAVA ORS® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). In 2024, the FDA granted RADICAVA ORS Orphan Drug Exclusivity based on its major contribution to patient care by providing an oral suspension route of administration that avoids the burdens of IV administration. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. Each 105 mg (5mL) dose of RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1
Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021), Malaysia (December 2021), Australia (February 2023) and Brazil (February 2024). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA ORS, along with the previously available IV RADICAVA® (edaravone), have been used to treat over 19,000 people with ALS, with over 2.5-million days of therapy, and have been prescribed by over 2,600 HCPs.2-4
INDICATION
RADICAVA ORS® (edaravone) is indicated for the treatment of amyotrophic lateral sclerosis (ALS).
IMPORTANT SAFETY INFORMATION
Hypersensitivity Reactions
RADICAVA ORS® (edaravone) is contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred.
Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA ORS, treat per standard of care, and monitor until the condition resolves.
Sulfite Allergic Reactions
RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people.
Adverse Reactions
The most common adverse reactions (≥10%) reported in RADICAVA® (edaravone)-treated patients and at least 2% more frequently than placebo were contusion (15% vs 9%), gait disturbance (13% vs 9%), and headache (10% vs 6%), respectively. In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS.
Pregnancy
Based on animal data, RADICAVA ORS may cause fetal harm.
To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information, also available at www.RADICAVAORS.com.
About Mitsubishi Tanabe Pharma America, Inc.
Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit www.mt-pharma-america.com or follow us on X (formerly Twitter), Facebook and LinkedIn.
About Mitsubishi Tanabe Pharma Corporation
Mitsubishi Tanabe Pharma Corporation (MTPC) is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MTPC sets the MISSION of "Creating hope for all facing illness." To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to https://www.mt-pharma.co.jp/e/.
Media inquiries:
Media_MTPA@mt-pharma-us.com
1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022
2 Data on file. Mitsubishi Tanabe Pharma America, Inc.
3 Data on file. Mitsubishi Tanabe Pharma America, Inc.
4 Data on file. Mitsubishi Tanabe Pharma America, Inc.
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