ALS experts share their experiences with RADICAVA^®

This video is sponsored by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The speaker is presenting on behalf of, and has received compensation from MTPA.

RADICAVA ORS^® Treatment Initiation Checklist

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RADICAVA ORS^® recognized as a MAJOR CONTRIBUTION TO PATIENT CARE by the FDA.¹ Request a rep visit.

Efficacy of RADICAVA^®

RADICAVA ORS^® (edaravone)
has the same efficacy as RADICAVA^® (edaravone) IV²

THE DIFFERENCE IS EXPERIENCE

RADICAVA ORS^® is recognized by the FDA as a major contribution to patient care due to its oral route of administration offering a less burdensome option vs intravenous administration¹

REVIEW RADICAVA ORS^® CLINICAL HISTORY

RADICAVA ORS^® offers the same drug as RADICAVA^® IV in a different formulation^2,3

Results from a phase 1 pharmacokinetic study in healthy subjects showed equivalent plasma levels with RADICAVA ORS^® and RADICAVA^® IV.^2,3

Mean Plasma Concentration-Time Profiles of Unchanged Edaravone for RADICAVA ORS^® and RADICAVA^® IV³

Mean Plasma Concentration Time Profiles of Unchanged Edaravone for RADICAVA® (edaravone)

STUDY DESIGN

The pivotal phase 3 trial for RADICAVA^® was a 24-week, randomized, placebo-controlled study²

Study Design From the Pivotal Phase 3 Trial for RADICAVA^{®4,5,a (see footnote)}

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

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

91.3%

RADICAVA^®
(n=63/69)

91.2%

Placebo
(n=62/68)

STUDY DESIGN

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

At study entry^4,7
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^{8,b (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

In the pivotal phase 3 clinical trial, RADICAVA^® showed a 33% change in the slope of the ALSFRS-R vs placebo.^2,4

Physical Function in Daily Activities at 24 Weeks^2,4

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

33% less change in ALSFRS-R scores from baseline vs placebo at 24 weeks^2,4

A report on a survey of 65 members of Northeast ALS Consortium (NEALS) concluded that a treatment is clinically meaningful when it results in 20% to 25% or greater change in the slope of ALSFRS-R reflecting the slowing of functional decline.⁹

STUDY DESIGN

In the pivotal phase 3 study, the P value was calculated based on the results

It’s important to note a treatment difference of 2.49-point change from baseline in ALSFRS-R (0.99, 3.98) with P=0.0013 is considered statistically significant.¹⁰

To put the results in context, consider what P values suggest and how probable the results are due to chance.¹¹

Very strong statistical differenceP<0.001

That means that there is less than 1 in 1000 probability that the results are due to random chance

Statistical differenceP≤0.05

That means that there is less than 5% probability that the results were due to random chance

No statistical differenceP>0.05

No statistical difference
between groups

In the pivotal phase 3 clinical trial, patients on RADICAVA^® declined slower vs placebo.⁴

Physical Function in Daily Activities at 24 Weeks^2,4

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

91.3%

RADICAVA^® IV
(n=63/69)

91.2%

Placebo
(n=62/68)

ABOUT THE ALSFRS-R STUDY DESIGN

Patients on RADICAVA^® lost fewer points vs placebo²

In the phase 3 clinical trial, RADICAVA^® was shown to slow the decline of physical function in patients with ALS.²

Percent of Patients Who^2,12:

Bar graph showing percentage of patients who lost ALSFRS-R points in RADICAVA® (edaravone) clinical trial

“…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.”¹²

STUDY DESIGN

At 24 weeks, there was an overall shift in point loss between treatment groups.¹²

A similar number of patients in both the RADICAVA^® arm and placebo arm lost 3 to 10 points.¹²

It is very important to let patients know that²:

RADICAVA ORS^® is an ongoing treatments 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 critical in slowing the loss of physical function.^2,4,14

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

Learn More

^aPatients who completed the observation period were randomized to RADICAVA^® or placebo.³ Return to content

^bJapan ALS severity classification grades, which were used for the pivotal clinical trial (J19), range from 1 to 5 as follows⁷:

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

FVC=forced vital capacity; QD=once daily.

References: 1. US Food and Drug Administration. Clinical superiority findings. Accessed April 11, 2024. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/clinicalsuperiority-findings 2. RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022. 3. 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. 4. 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;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. Data on file. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc. 7. ClinicalTrials.gov. Phase 3 study of MCI-186 for treatment of amyotrophic lateral sclerosis. Accessed January 6, 2022. https://clinicaltrials.gov/ct2/show/NCT01492686 8. Kalin A, Medina-Paraiso E, Ishizaki K, et al. A safety analysis of edaravone (MCI-186) during the first six cycles (24 weeks) of amyotrophic lateral sclerosis (ALS) therapy from the double-blind period in three randomized, placebo-controlled studies. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(suppl 1):71-79. 9. Castrillo-Viguera C, Grasso DL, Simpson E, et al. Clinical significance in the change of decline in ALSFRS-R. Amyotroph Lateral Scler. 2010;11(1-2):178-180. 10. 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;16(7):505-512. 11. Singh P. P value, statistical significance and clinical significance. J Clin Prev Cardiol. 2013;2(4):202-204. 12. 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. 13. Grad LI, Rouleau GA, Ravits J, et al. Clinical spectrum of amyotrophic lateral sclerosis (ALS). Cold Spring Harb Perspect Med. 2017;7(8):a024117. 14. 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.

Efficacy of RADICAVA^®

RADICAVA ORS^® offers the same drug as RADICAVA^® IV in a different formulation^2,3

Mean Plasma Concentration-Time Profiles of Unchanged Edaravone for RADICAVA ORS^® and RADICAVA^® IV³

The pivotal phase 3 trial for RADICAVA^® was a 24-week, randomized, placebo-controlled study²

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

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:

In the pivotal phase 3 clinical trial, RADICAVA^® showed a 33% change in the slope of the ALSFRS-R vs placebo.^2,4

In the pivotal phase 3 study, the P value was calculated based on the results

In the pivotal phase 3 clinical trial, patients on RADICAVA^® declined slower vs placebo.⁴

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

Patients on RADICAVA^® lost fewer points vs placebo²

Percent of Patients Who^2,12:

At 24 weeks, there was an overall shift in point loss between treatment groups.¹²

A similar number of patients in both the RADICAVA^® arm and placebo arm lost 3 to 10 points.¹²

It is very important to let patients know that²:

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

Sulfite Allergic Reactions

Adverse Reactions

Pregnancy

INDICATION

You are now leaving RADICAVAHCP.com

Efficacy of RADICAVA®

RADICAVA ORS® offers the same drug as RADICAVA® IV in a different formulation2,3

Mean Plasma Concentration-Time Profiles of Unchanged Edaravone for RADICAVA ORS® and RADICAVA® IV3

The pivotal phase 3 trial for RADICAVA® was a 24-week, randomized, placebo-controlled study2

Most patients in the RADICAVA® and placebo arms were on riluzole4,6

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:

In the pivotal phase 3 clinical trial, RADICAVA® showed a 33% change in the slope of the ALSFRS-R vs placebo.2,4

In the pivotal phase 3 study, the P value was calculated based on the results

In the pivotal phase 3 clinical trial, patients on RADICAVA® declined slower vs placebo.4

Most patients in the RADICAVA® and placebo arms were on riluzole4,6

Patients on RADICAVA® lost fewer points vs placebo2

Percent of Patients Who2,12:

At 24 weeks, there was an overall shift in point loss between treatment groups.12

A similar number of patients in both the RADICAVA® arm and placebo arm lost 3 to 10 points.12

It is very important to let patients know that2:

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

Sulfite Allergic Reactions

Adverse Reactions

Pregnancy

INDICATION

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

Sulfite Allergic Reactions

Adverse Reactions

Pregnancy

INDICATION

You are now leaving RADICAVAHCP.com

Efficacy of RADICAVA^®

RADICAVA ORS^® offers the same drug as RADICAVA^® IV in a different formulation^2,3

Mean Plasma Concentration-Time Profiles of Unchanged Edaravone for RADICAVA ORS^® and RADICAVA^® IV³

The pivotal phase 3 trial for RADICAVA^® was a 24-week, randomized, placebo-controlled study²

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

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:

In the pivotal phase 3 clinical trial, RADICAVA^® showed a 33% change in the slope of the ALSFRS-R vs placebo.^2,4

In the pivotal phase 3 clinical trial, patients on RADICAVA^® declined slower vs placebo.⁴

Most patients in the RADICAVA^® and placebo arms were on riluzole^4,6

Patients on RADICAVA^® lost fewer points vs placebo²

Percent of Patients Who^2,12:

At 24 weeks, there was an overall shift in point loss between treatment groups.¹²

A similar number of patients in both the RADICAVA^® arm and placebo arm lost 3 to 10 points.¹²

It is very important to let patients know that²: