Drug Trials Snapshots: RADICAVA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to RADICAVA Prescribing Information for complete information.
RADICAVA (edaravone)
Ra di ká vah
Mitsubishi Tanabe Pharma Corporation
Approval date: May 5, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
RADICAVA is a drug for the treatment of Amyotrophic Lateral Sclerosis (ALS).
ALS (also known as Lou Gehrig’s disease) is a rare disease that affects nerve cells in the brain and the spinal cord leading to progressive muscle weakness and premature death.
How is this drug used?
RADICAVA is given by a healthcare provider using a needle placed in a vein (known as intravenous infusion). It takes about 60 minutes to receive the full dose of RADICAVA.
RADICAVA is administered in treatment cycles.
What are the benefits of this drug?
After 24 weeks, patients taking RADICAVA showed less decline in their ability to perform daily functional activities than the patients who received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the trial that established the efficacy of RADICAVA (Trial 1). The primary efficacy endpoint was a comparison of the change between treatment arms in the ALS Functional Rating Scale – Revised (ALSFRS-R) total scores from Baseline to the end of Cycle 6 (Week 24). The ALSFRS-R scale consists of 12 questions that evaluate fine motor, gross motor, bulbar, and respiratory function of patients. Each item is scored from 0-4, with higher scores representing greater functional ability.
Table 2. Analysis of Change from Baseline at the End of Cycle 6 in ALSFRS-R Scores
| Treatment | N | Change from Baseline LS Mean ± SE (95% CI) | Treatment Difference (RADICAVA – placebo [95% CI]) | p-value |
|---|---|---|---|---|
| RADICAVA | 69 | −5.01±0.64 | 2.49 (0.99, 3.98) | 0.0013 |
| Placebo | 68 | −7.50±0.66 |
RADICAVA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: RADICAVA worked similarly in men and women.
- Race: All patients were Asian; therefore differences in response to RADICAVA among races could not be determined.
- Age: RADICAVA worked similarly in patients below and above 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Tables below summarize efficacy results by sex and age subgroups. These analyses are exploratory and therefore should be interpreted with caution. Race subgroups could not be tested because all participants were Asian.
Table 3. Estimated Treatment Difference on ALSFRS-R at Cycle 6 by Sex
| Sex | Estimated Treatment Difference | Standard Error |
|---|---|---|
| Men | -2.85 | 1.10 |
| Women | -2.76 | 1.18 |
Adapted from FDA Statistical review
Table 4. Estimated Treatment Difference on ALSFRS-R at Cycle 6 by Age Group
| Age Group | Estimated Treatment Difference | Standard Error |
|---|---|---|
| 65> | -2.74 | 0.94 |
| ≥65 years | -3.00 | 1.34 |
Adapted from FDA Statistical review
What are the possible side effects?
RADICAVA may cause serious allergic reactions.
The most common side effects of RADICAVA are bruising (contusion), gait disturbance, and headache.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions that occurred in at least 2% of RADICAVA treated patients in pooled placebo-controlled trials in patients with ALS.
Table 5. Adverse Reactions that Occurred in ≥ 2% of RADICAVA-Treated Patients and More Frequently than in Placebo-Treated Patients (safety population)
| Adverse Reaction | RADICAVA (N=184) % | Placebo (N=184) % |
|---|---|---|
| Contusion | 15 | 9 |
| Gait disturbance | 13 | 9 |
| Headache | 10 | 6 |
| Dermatitis | 8 | 5 |
| Eczema | 7 | 4 |
| Respiratory failure, respiratory disorder, hypoxia | 6 | 4 |
| Glycosuria | 4 | 2 |
| Tinea infection | 4 | 2 |
RADICAVA Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: All the patients were Asian; therefore differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in patients below and above 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Tables below summarize safety results by sex and age subgroups. These analyses are exploratory and therefore should be interpreted with caution. Race subgroups could not be tested because all the participants were Asian participation.
Table 6. Adverse Reactions by Sex that Occurred in at least 5% of the Patients (safety population)
| Preferred Term (PT) | Men | Women | ||
|---|---|---|---|---|
| RADICAVA (n=109) | Placebo (n=116) | RADICAVA (n=75) | Placebo (n=68) | |
| Gait disturbance | 16 (15) | 13 (11) | 7 (9) | 4 (6) |
| Contusion | 11 (10) | 8 (7) | 16 (21) | 8 (12) |
| Headache | 6 (6) | 6 (5) | 9 (12) | 4 (6) |
Clinical trial data
Table 7. Adverse Reactions by Age group that Occurred in at least 5% of the Patients (safety population)
| Preferred Term (PT) | 65=""> | ≥ 65 years | ||
|---|---|---|---|---|
| RADICAVA (n=131) | Placebo (n=127) | RADICAVA (n=53) | Placebo (n=57) | |
| Gait disturbance | 18 (14) | 9 (7) | 5 (9) | 8 (14) |
| Contusion | 19 (15) | 11 (9) | 8 (15) | 5 (9) |
| Headache | 12 (9) | 8 (6) | 3 (6) | 2 (4) |
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved RADICAVA based on evidence from three clinical trials of 368 patients with ALS. The trials were conducted in Japan.
These 368 patients represent the population that was used to assess the side effects of RADICAVA (called the safety population) and will be presented in the figures below.
Some of these patients (total of 137 patients) represent the population that was used to establish the benefit of RADICAVA. These patients are presented in Table 9 under MORE INFO section.
The figure below summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex (safety population)
Clinical trial data
Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trials.
Figure 2. Baseline Demographics by Race (safety population)
Clinical trial data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| Asian | 368 | 100 |
| White | 0 | 0 |
| Black or African American | 0 | 0 |
Clinical trial data
Figure 3 summarizes the percentage of patients by age in the clinical trials.
Figure 3. Baseline Demographics by Age (safety population)
Clinical trial data
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials.
Table 8. Baseline Demographics of Patients in the Clinical Trials (safety population)
| RADICAVA (N=184) n (%) | Placebo (N=184) n (%) | Total (N=368) n (%) | ||
|---|---|---|---|---|
| Sex | ||||
| Men | 109 (59) | 116 (63) | 225 (61) | |
| Women | 75 (41) | 68 (37) | 143 (39) | |
| Age (years) | ||||
| Min, Max | 29,75 | 28,75 | 28,75 | |
| Median | 60 | 60 | 60 | |
| Age Group | ||||
| 65> | 131 (71) | 127 (69) | 258 (70) | |
| ≥65 years | 53 (29) | 57 (31) | 110 (30) | |
| Race | ||||
| Asian | 184 (100) | 184 (100) | 368 (100) | |
| Geographic Region | ||||
| Japan | 184 (100) | 184 (100) | 368 (100) | |
Clinical trial data
Table 9. Baseline Demographics of Patients in the Clinical Trial 1 (efficacy population)
| RADICAVA (N=69) n (%) | Placebo (N=68) n (%) | Total (N=137) n (%) | ||
|---|---|---|---|---|
| Sex | ||||
| Men | 38 (55) | 41 (60) | 79 (58) | |
| Women | 31 (45) | 27 (40) | 58 (42) | |
| Age (years) | ||||
| Min, Max | 30, 75 | 38, 75 | 30, 75 | |
| Median | 62 | 62 | 62 | |
| Age Group | ||||
| 65> | 46 (67) | 46 (68) | 92 (67) | |
| ≥65 years | 23 (33) | 22 (32) | 45 (33) | |
| Race | ||||
| Asian | 69 (100) | 68 (100) | 137 (100) | |
| Geographic Region | ||||
| Japan | 69 (100) | 68 (100) | 137 (100) | |
Clinical trial data
How were the trials designed?
The side effects of RADICAVA were evaluated in three clinical trials of patients with ALS. Most of the patients continued taking their usual medications for ALS during the trial. All patients received treatment with either RADICAVA or placebo during the trials. Neither the patients nor the health care providers knew which new treatment was being given until the trials were completed 24 weeks later.
The benefit of RADICAVA was established in one of these three trials by measuring the change in patients’ abilities to perform activities of daily living from the beginning to the end of the trial and comparing it to placebo.
How were the trials designed?
The safety of RADICAVA was evaluated in 3 randomized, double-blind, placebo-controlled trials of 6 months duration conducted in Japan.
One of these trials (Trial 1) was used to establish the efficacy of RADICAVA. Patients in this trial had a probable or definite ALS diagnosis based on the El Escorial revised diagnostic criteria for ALS and disease duration of 2 years or less. RADICAVA was administered in 6 treatment cycles. The primary efficacy endpoint was a comparison of the change between treatment arms in the ALS Functional Rating Scale-Revised (ALSFRS-R) total scores from Baseline to the end of Cycle 6 (Week 24). The ALSFRS-R scale consists of 12 questions that evaluate fine motor, gross motor, bulbar, and respiratory function. Each item is scored from 0-4, with higher scores representing greater functional ability.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.