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RADICAVA ORS^® Treatment Initiation Checklist

REVIEW THE PIVOTAL STUDY DATA FOR RADICAVA^® AND THE RESULTS FROM A RETROSPECTIVE ANALYSIS FOR RADICAVA ORS^® REVIEW NOW

Efficacy of RADICAVA^®

For your appropriate patients, initiate treatment with RADICAVA ORS^® (edaravone) upon diagnosis.¹

RADICAVA ORS^®: EQUIVALENT TO RADICAVA^® as shown in phase 1 pharmacokinetic study plasma levels in healthy subjects under fasting conditions²

RADICAVA ORS^® has the same efficacy as RADICAVA^® (edaravone)—an FDA-approved treatment shown in a pivotal phase 3 clinical trial to help slow the loss of physical function in ALS^3,4

Data from Pivotal Phase 3 Study MCI-186-J19

RADICAVA^® study design: a 24-week randomized, placebo-controlled study³

Cycles of 24-week double blind study of RADICAVA® (edaravone) versus placebo

The pivotal phase 3 clinical trial was specifically designed to measure change in physical function assessed by the ALSFRS-R^4-6

STUDY DESIGN

Patients were selected for relatively good function at baseline and adequate disease progression on the ALSFRS-R⁴

At study entry³
Definite ALS or probable ALS (El Escorial and revised Airlie House diagnostic criteria)
Scores ≥2 on all items of the ALSFRS-R
Grade 1 or 2 in Japan ALS severity classification^{a (see foonote)}
Normal respiratory function (≥80% FVC)
Disease duration ≤2 years
Age 20-75

Deterioration in ALSFRS-R score of 1 to 4 points during 12-week pre-study observation period

The inclusion criteria of the pivotal clinical trial⁴:

Used a defined population based on an analysis of an earlier clinical trial

Identified patients who would be expected to have a sufficient and measurable deterioration over 24 weeks in order to see a treatment effect

RADICAVA ORS^®: a treatment proven to help slow functional decline^3,4

Data from pivotal phase 3 clinical trial

On average, patients on RADICAVA^® lost 2.49 fewer points on the ALSFRS-R vs placebo^3,4

Physical Function in Daily Activities at 24 Weeks^3,4

Line graph showing reduction in ALSFRS-R score for RADICAVA® (edaravone) versus Placebo from baseline to week 24.

Over 90% of patients in each group were also being treated with riluzole.^4,7

STUDY DESIGN

3X as many patients given RADICAVA^® lost ≤2 points
(39.1% RADICAVA^® vs 13.2% placebo).^3,8

“…the overall distribution shift suggests that the effect of slowing decline…was driven by the majority of patients responding to treatment rather than a response to treatment that was limited to a specific subtype of patient.”¹⁰

Takei K, Takahashi F, Liu S, et al. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(suppl1):49-54.

Decline in ALSFRS-R points over time

Pivotal phase 3 study

Physical Function in Daily Activities at 24 Weeks^4,7

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,7

91.3%

RADICAVA^®
(n=63/69)

91.2%

Placebo
(n=62/68)

STUDY DESIGN ABOUT THE ALSFRS-R

Retrospective Analysis—ALSFRS-R change over 48 weeks

Takahashi F, Genge A, Hirai M, et al. The Pooled Resource Open-Access ALS Clinical Trials Consortium. Muscle Nerve. July 2025.*

Limitations

This was a retrospective, external control analysis comparing patients from the RADICAVA ORS^® clinical trials with historical placebo patients from the PRO-ACT database. Although propensity score matching was used to reduce bias, the analysis remains subject to limitations inherent to non-randomized comparisons, including potential residual confounding due to unmeasured or inadequately balanced variables. Differences in trial protocols, data collection methods, and supportive care over time may also limit comparability
These data are considered exploratory. No adjustments were made for multiplicity, and the findings should be interpreted with caution given the retrospective nature of the analysis and use of external controls. Thus, no definitive conclusions can be drawn

*Data used in the preparation of this article were obtained from the PRO-ACT database. As such, the following organizations and individuals within the PRO-ACT Consortium contributed to the design and implementation of the PRO-ACT database and/or provided data, but did not participate in the analysis of the data or the writing of this report: ALS Therapy Alliance; Cytokinetics; Amylyx Pharmaceuticals; Knopp Biosciences; Neuraltus Pharmaceuticals; Neurological Clinical Research Institute at Mass General; Northeast ALS Consortium (NEALS); Novartis; Orion Corporation; Prize4Life Israel; Regeneron Pharmaceuticals, Inc.; Sanofi; Teva Pharmaceutical Industries Ltd.; The ALS Association; and the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.

Key points covered in detail below

These PRO-ACT analyses are consistent with and provide additional supportive evidence to previously published studies.

They further demonstrate that RADICAVA ORS^® helps slow functional decline in patients with ALS and include geographically and ethnically diverse populations from North America, Europe, and Asia.⁹

Expanding on existing evidence from the pivotal study (MCI-186-J19)

RADICAVA ORS^® was investigated in clinical trials MT-1186-A01/A02/A03/A04.

While study J19 was conducted in a Japanese patient population with RADICAVA^®, studies A01/A02/A03/A04 were conducted with RADICAVA ORS^® in geographically and racially diverse patient populations.

RADICAVA ORS^® studies included in the retrospective analyses

Study MT-1186-A01

Study design:

A phase 3, global, multicenter, open-label study that evaluated the long-term safety and tolerability of RADICAVA ORS^® 105 mg on/off dosing regimen over 48 weeks. The study enrolled 185 patients with ALS who had a baseline forced vital capacity ≥70% of predicted and disease duration ≤3 years.^9,10

Results:

RADICAVA ORS^® was well tolerated during 48 weeks of treatment, with no new safety concerns identified. The most common treatment-emergent adverse events (TEAEs) at week 48 were fall (22.2%), muscular weakness (21.1%), and constipation (17.8%).¹⁰

Study MT-1186-A03

Study design:

Provided up to 96 weeks of additional treatment in 124 patients with ALS who completed the initial 48 weeks of study MT-1186-A01.^9,11

Results:

RADICAVA ORS^® was well tolerated with no new safety concerns. The most common TEAEs were fall (16.9%), muscular weakness (14.5%), dyspnea (13.7%), constipation (12.9%), and dysphagia (12.1%). These TEAEs were consistent with the safety profile for RADICAVA from previous clinical trials.¹¹

Study MT-1186-A02

Study design:

A phase 3b, multicenter, double-blind, parallel-group, randomized study that evaluated whether investigational, once-daily RADICAVA ORS^® 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 383 patients with ALS. The study enrolled 384 patients who had definite or probable ALS, baseline forced vital capacity ≥70%, and baseline disease duration ≤2 years. This study was a post-marketing commitment following the FDA approval of RADICAVA^® (edaravone).^9,12

Results:

At week 48, the once-daily regimen did not show superiority to the FDA-approved on/off dosing regimen based on the primary efficacy endpoint of CAFS score, as there was no statistically significant difference between the 2 treatment groups. RADICAVA ORS^® was generally well tolerated and no new safety concerns were identified in either group.¹²

Study MT-1186-A04

Study design:

Provided up to 48 weeks of additional treatment in 192 patients with ALS who completed the initial 48 weeks of study MT-1186-A02.^9,12

Results:

At week 96, once-daily dosing did not show a statistically significant difference vs FDA-approved on/off dosing in time to ≥12-point decrease in ALSFRS-R or death. RADICAVA ORS^® was generally well tolerated and no new safety concerns were identified in either group.¹²

PRO-ACT analysis methods

RADICAVA ORS was investigated in clinical trials MT-1186-A01/A02/A03/A04

Patients from studies A02/A04 (prespecified analysis) and studies A01/A02/A03/A04 (post hoc analysis) were propensity score matched 1:1 on 10 baseline variables with historical PRO-ACT placebo patients to assess the impact of RADICAVA ORS^® on function
To account for imbalances in participant characteristics between each group, patients were propensity score matched to adjust for baseline covariates
Data for the historical, external control patients with ALS who had not received active investigational treatment but may have received riluzole in their respective clinical trials were obtained from the PRO-ACT database⁹

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
Finding A Cure
The ALS Association

The 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

Key inclusion criteria

In the prespecified primary analysis cohort (A02/A04), the following key inclusion criteria were applied for both treated and PRO-ACT placebo groups⁹:

Definite ALS or probable ALS per El Escorial revised Airlie House diagnostic criteria
≥18 to 75 years of age
≥2 points on each individual ALSFRS-R item at baseline
≥70% respiratory function (baseline % FVC or % SVC)
≤2 years between first symptom of ALS and informed consent
1- to 4-point decline in total ALSFRS-R score during 8 weeks (±7 days) between screening and baseline visits (RADICAVA ORS^®-treated group only)

Endpoint for data shown on this page

Change in ALSFRS-R score from baseline up to week 48⁹

Results: ALSFRS-R functional change

Endpoint: change in ALSFRS-R score from baseline up to 48 weeks

In the primary propensity score–matched analysis cohort (N=156), change from baseline ALSFRS-R score in patients in the combined RADICAVA ORS^® (edaravone) (n=78) vs PRO-ACT placebo (n=78) groups were examined
Patients in both groups had a mean baseline ALSFRS-R score of 41.0 points (Table 1, Figure 1)⁹

Table 1: From baseline ALSFRS-R to total score change in cohort groups at week 48⁹

Table 1: From baseline ALSFRS-R to total score change in cohort groups at week 489

The LS mean ± SE ALSFRS-R total score change from baseline to week 48 was smaller in the combined RADICAVA ORS^® group (-8.4 ± 1.0 points) vs PRO-ACT placebo group (-14.1 ±1.0 points).

LIMITATION: These data are considered exploratory. No adjustments were made for multiplicity, and the findings should be interpreted with caution given the retrospective nature of the analysis and use of external controls. Thus, no definitive conclusions can be drawn.

Comparison of ALSFRS-R functional change at 48 weeks

Figure 1: ALSFRS-R total score change over 48 weeks in the propensity score–matched combined study A02 and A04 RADICAVA ORS^® group vs PRO-ACT placebo group⁹

ALSFRS-R total score change over 48 weeks in the propensity score–matched combined study A02 and A04 RADICAVA ORS<sup>®</sup> group vs PRO-ACT placebo group

Post hoc analysis in a broader population

In the post hoc propensity score–matched analysis cohort that included the broader group of ALS patients from studies A01/A02/A03/A04, patients in the RADICAVA ORS^® group (n=210) vs PRO-ACT placebo group (n=210) started at a mean baseline ALSFRS-R score of 39.1 and 38.9 points, respectively⁹
At week 48, the LS mean (± SE) change from baseline in ALSFRS-R total score was −10.5 ± 0.7 points in the RADICAVA ORS^® group and −12.9 ± 0.6 points in the PRO-ACT placebo group⁹

It is very important to let patients know that³:

RADICAVA ORS^® is an ongoing treatment for ALS
It is not a cure
It does not restore function
Individual results may vary

ALS can progress rapidly.¹³ Beginning treatment with RADICAVA ORS^® can be meaningful in slowing the loss of physical function.^4,14

RADICAVA ORS^®—the ONLY FDA-approved oral form of edaravone—was built on years of clinical research and development

Learn More

^aJapan ALS severity classification grades, which were used for the pivotal clinical trial (J19), range from 1 to 5 as follows¹²:

1. Able to work or perform housework. 2. Independent living but unable to work. 3. Requiring assistance for eating, excretion, or ambulation. 4. Presence of respiratory insufficiency, difficulty in coughing out sputum, or dysphagia. 5. Using a tracheostomy tube, tube feeding, or tracheostomy positive-pressure ventilation. Return to content

ADL=activities of daily living; BL=baseline; FVC=forced vital capacity; LS=least squares; QD=once daily; SE=standard error.

References: 1. Leigh PN, Swash M, Iwasaki Y, et al. Amyotrophic lateral sclerosis: a consensus viewpoint on designing and implementing a clinical trial. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5(2):84-98. 2. Shimizu H, Nishimura Y, Shiide Y, et al. Bioequivalence study of oral suspension and intravenous formulation of edaravone in healthy adult subjects. Clin Pharmacol Drug Dev. 2021;10(10):1188-1197. 3. RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Tanabe Pharma America, Inc.; 2025. 4. Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017 Jul;16(7):505-512. 5. Takei K, Tsuda K, Takahashi F, et al. Post-hoc analysis of open-label extension period of study MCI186-19 in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(suppl 1):64-70. 6. Cedarbaum JM, Stambler N, Malta E, et al; BDNF ALS Study Group (Phase III). The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J Neurol Sci. 1999;169(1-2):13-21. 7. Data on file. Tanabe Pharma America, Inc. 8. Takei K, Takahashi F, Liu S, et al. Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(suppl 1):49-54. 9. Takahashi F, Genge A, Hirai M, et al. 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. Muscle Nerve. Published online July 1, 2025. doi:10.1002/mus.28462 10. Genge A, Pattee GL, Sobue G, et al. Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48 weeks of treatment. Muscle Nerve. 2023;67:124-129. 11. Genge A, Pattee GL, Sobue G, et al. Safety extension study of edaravone oral suspension in patients with amyotrophic lateral sclerosis for up to an additional 96 weeks of treatment. Muscle Nerve. Published online June 9, 2025. doi:10.1002/mus.28451 12. Rothstein J, Genge A, De Silva S, et al. Efficacy and safety of once daily dosing vs approved on/off dosing of edaravone oral suspension up to 48 weeks in patients with amyotrophic lateral sclerosis (study MT-1186-A02). Muscle Nerve. Published online June 6, 2025. doi:10.1002/mus.28448 13. Sawada H. Considerations for pharmacotherapy use in patients with amyotrophic lateral sclerosis: the earlier it starts, the better the results. Expert Opin Pharmacother. 2019;20(14):1671-1674. 14. Samadhiya S, Sardana V, Bhushan B, et al. Assessment of therapeutic response of edaravone and riluzole combination therapy in amyotrophic lateral sclerosis patients. Ann Indian Acad Neurol. 2022;25(4):692-697.

Efficacy of RADICAVA®

RADICAVA ORS®: EQUIVALENT TO RADICAVA® as shown in phase 1 pharmacokinetic study plasma levels in healthy subjects under fasting conditions2

Data from Pivotal Phase 3 Study MCI-186-J19

RADICAVA® study design: a 24-week randomized, placebo-controlled study3

Patients were selected for relatively good function at baseline and adequate disease progression on the ALSFRS-R4

The inclusion criteria of the pivotal clinical trial4:

RADICAVA ORS®: a treatment proven to help slow functional decline3,4

On average, patients on RADICAVA® lost 2.49 fewer points on the ALSFRS-R vs placebo3,4

3X as many patients given RADICAVA® lost ≤2 points(39.1% RADICAVA® vs 13.2% placebo).3,8

Pivotal phase 3 study

Most patients in the RADICAVA® and placebo arms were on riluzole4,7

Retrospective Analysis—ALSFRS-R change over 48 weeks

Limitations

Key points covered in detail below

Expanding on existing evidence from the pivotal study (MCI-186-J19)

Study MT-1186-A01

Study design:

Results:

Study MT-1186-A03

Study design:

Results:

Study MT-1186-A02

Study design:

Results:

Study MT-1186-A04

Study design:

Results:

RADICAVA ORS was investigated in clinical trials MT-1186-A01/A02/A03/A04

About the PRO-ACT database

Key inclusion criteria

Endpoint for data shown on this page

Results: ALSFRS-R functional change

Endpoint: change in ALSFRS-R score from baseline up to 48 weeks

Table 1: From baseline ALSFRS-R to total score change in cohort groups at week 489

Comparison of ALSFRS-R functional change at 48 weeks

Figure 1: ALSFRS-R total score change over 48 weeks in the propensity score–matched combined study A02 and A04 RADICAVA ORS® group vs PRO-ACT placebo group9

Post hoc analysis in a broader population

It is very important to let patients know that3:

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

Sulfite Allergic Reactions

Adverse Reactions

Pregnancy

INDICATION

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

Sulfite Allergic Reactions

Adverse Reactions

Pregnancy

INDICATION

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Efficacy of RADICAVA^®

RADICAVA ORS^®: EQUIVALENT TO RADICAVA^® as shown in phase 1 pharmacokinetic study plasma levels in healthy subjects under fasting conditions²

RADICAVA^® study design: a 24-week randomized, placebo-controlled study³

Patients were selected for relatively good function at baseline and adequate disease progression on the ALSFRS-R⁴

The inclusion criteria of the pivotal clinical trial⁴:

RADICAVA ORS^®: a treatment proven to help slow functional decline^3,4

On average, patients on RADICAVA^® lost 2.49 fewer points on the ALSFRS-R vs placebo^3,4

3X as many patients given RADICAVA^® lost ≤2 points
(39.1% RADICAVA^® vs 13.2% placebo).^3,8

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,7

Table 1: From baseline ALSFRS-R to total score change in cohort groups at week 48⁹

Figure 1: ALSFRS-R total score change over 48 weeks in the propensity score–matched combined study A02 and A04 RADICAVA ORS^® group vs PRO-ACT placebo group⁹

It is very important to let patients know that³: