Efficacy

Explore the pivotal clinical trial for RADICAVA® (edaravone), including how it was designed and the results.

Study Design

The study design of the pivotal clinical trial evaluated RADICAVA® vs placebo over 24 weeks1


Pivotal Study Design1,2

study design chart showing no treatment during observation period and RADICAVA® (edaravone) and placebo in pivotal trial study design chart showing no treatment during observation period and RADICAVA® (edaravone) and placebo in pivotal trial

Patients who completed the observation period were randomized to RADICAVA® or placebo.1

In the pivotal clinical trial for RADICAVA®
Most patients in the RADICAVA® and placebo arms took riluzole2

91.3%RADICAVA®
(n=63)
91.2%Placebo
(n=62)

Inclusion criteria of the pivotal clinical trial


At study entry1,3
Definite or Probable ALS (El Escorial revised and Airlie House diagnostic criteria)
Scores ≥2 on all items of the ALSFRS-R
Grade 1 or 2 Japan ALS severity classificationa
Normal respiratory function (≥80% FVC)
Disease duration ≤2 years
Age 20-75
At randomization3
Deterioration in ALSFRS-R score during 12-week pre-study observation period of 1 to 4 points

The inclusion criteria4:

  • Used a defined population based on an analysis of an earlier trial
  • Identified patients who would be expected to have a sufficient and measurable deterioration over 24 weeks in order to see the effect of treatment

aJapan ALS severity classification grades, which were used for the pivotal clinical trial (J19), range from 1 to 5 as follows5:

  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

 FVC=forced vital capacity.


The enrichment strategy for Study 19 resulted in patients with relatively good function at baseline and adequate disease progression on the ALSFRS-R scale.

Slowing Loss of Physical Function

In the pivotal clinical trial, RADICAVA® demonstrated a 33% less change in ALSFRS-R scores from baseline vs placebo at 24 weeks1

A report concerning a survey of 65 members of the NEALS Consortium concluded that a treatment that resulted in a 20%-25% or greater change in the slope of the ALSFRS-R is clinically meaningful.6


Physical Function in Daily Activities at 24 Weeks1

Change from Baseline
LS Mean ± SE

efficacy bar chart comparing placebo to RADICAVA® (edaravone) in pivotal trial efficacy bar chart comparing placebo to RADICACA® (edaravone) in pivotal trial

In the pivotal clinical trial, there was

33%

less change in ALSFRS-R scores from baseline vs placebo at 24 weeks.1



In the pivotal clinical trial, RADICAVA® patients declined slower vs placebo patients2

Physical Function in Daily Activities at 24 Weeks2

Mean change in ALSFRS-R Score (LOCF)
LS Mean ± SE

efficacy line chart comparing placebo to RADICAVA® (edaravone) in pivotal trial efficacy line chart comparing placebo to RADICAVA® (edaravone) in pivotal trial

In the pivotal clinical trial for RADICAVA®
Most patients in the RADICAVA® and placebo arms took riluzole2

91.3% RADICAVA®
(n=63)
91.2% placebo
(n=62)

Distribution of Change

Patients on RADICAVA® lost fewer points vs those on placebo1,7

In the clinical trial, RADICAVA® was shown to slow the decline of physical function in people with ALS.1 As shown below, 39.1% of patients in the RADICAVA® group declined 2 points or less vs 13.2% of those in the placebo group.7

Percent of patients who1,7:

distribution of change bar chart comparing placebo to RADICAVA® (edaravone) in pivotal trial distribution of change bar chart comparing placebo to RADICAVA® (edaravone) in pivotal trial

3X as many patients given RADICAVA® lost ≤2 points

(39.1% RADICAVA® vs 13.2% placebo)7


3X as many patients given placebo lost ≥11 points

(23.5% placebo vs 7.2% RADICAVA®)7

A similar number of patients in both the RADICAVA® arm and placebo arm lost 3 to 10 points.7

At 24 weeks, there was an overall shift in point loss between treatment groups7

Swipe on the chart to toggle between placebo and RADICAVA® data

Pointer

Number of placebo patients (n=68) who1,7:

distribution of change dot chart placebo

Number of RADICAVA® patients (n=69) who1,7:

distribution of change dot chart showing arm for RADICAVA® (edaravone), an FDA approved treatment option for ALS

Number of placebo patients (n=68) who1,7:

distribution of change dot chart placebo

Number of RADICAVA® patients (n=69) who1,7:

distribution of change dot chart showing arm for RADICAVA® (edaravone), an FDA approved treatment option for ALS

Combined charts:1,7

distribution of change dot chart comparing placebo to RADICAVA® (edaravone), an FDA approved treatment option for ALS

Tap the arrows to toggle between the graphs.

"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."7

Setting Expectations

Timeliness is essential

ALS patient standing next to his wife consulting with a neurologist (actor portrayals)

Because ALS can progress rapidly, beginning treatment as soon as possible can be important in slowing the decline of physical function.


It is very important to let patients know that1:

  • RADICAVA® is an ongoing treatment for ALS
  • It is not a cure
  • It does not restore function
  • Individual results may vary
    References:
  1. RADICAVA Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2018.
  2. Data on file. Mitsubishi Tanabe Pharma America, Inc.
  3. Takei K, Watanabe K, Yuki S, et al. Edaravone and its clinical development for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(sup1):5-10.
  4. Edaravone (MCI-186) ALS 16 Study Group. A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(sup1):11-19.
  5. 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(sup1):71-79.
  6. 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.
  7. Takei K, Takahashi F, Liu S, Tsuda K, Palumbo J. 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(sup1):49-54.
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Important Safety Information

Hypersensitivity Reactions

Radicava® (edaravone) is contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in Radicava®. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have been reported. Patients should be monitored carefully for hypersensitivity reactions, and if they occur, discontinue Radicava®, treat per standard of care, and monitor until the condition resolves.

Sulfite Allergic Reactions

Radicava® contains sodium bisulfite, and 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.

Most Common Adverse Reactions

Most common adverse reactions (at least 10% and greater than placebo) are contusion, gait disturbance, and headache.

Pregnancy

Based on animal data, Radicava® may cause fetal harm.

Geriatric Use

No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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.

Indication

Radicava® is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

Please see full Prescribing Information.

For more information about RADICAVA®, call 1-888-292-0058.