Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that causes muscle weakness, disability, and death. It is caused by gradual degeneration and eventual death of the upper and lower motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and to the muscles throughout the body. Death of the motor neurons inhibits signals from the brain to the muscles, resulting in muscle atrophy. Eventually, the brain loses the ability to initiate and control voluntary movements.
The median survival of those diagnosed with ALS is three to five years, with most individuals succumbing to respiratory failure. There are approximately 7000 new cases in the United States diagnosed each year. ALS has been found to have a higher rate of occurrence in Caucasians, and has an average age of onset of 62 years.
Edaravone (Radicava) was approved by the US Food and Drug Administration on May 5, 2017 for the treatment of amyotrophic lateral sclerosis (ALS). The mechanism by which edaravone (Radicava) exerts its therapeutic effect is unknown; however, since it is classified as a free radical scavenger, it is thought to block radicals that mediate neuronal and vascular damage.
The efficacy of edaravone (Radicava) was studied in trials. The initial trial was a six-month, randomized, placebo-controlled study in 205 Japanese individuals, with “definite” or “probable” ALS, with a duration of three years or less, as determined by the revised El Escorial (Airlie House) criteria. Individuals were excluded if they had reduced respiratory function, complications that require hospitalization, or were undergoing cancer treatment. This trial consisted of a 12-week pre-observation period, followed by a 24-week treatment period. The primary endpoint was the change in ALSFRS-R (ALS Functional Rating Scale- revised) score. The mean change in ALSFRS-R score during treatment was -5.70 in the edaravone (Radicava) group and -6.35 in the placebo group, demonstrating that the primary endpoint was not reached and, therefore, failed to establish efficacy of edaravone (Radicava) to delay the progression of ALS. A post hoc exploratory analysis was then done, and identified a subgroup of individuals in which edaravone (Radicava) may show effectiveness. This information was used to design another phase three clinical trial.
The second study was a six-month, randomized, placebo-controlled, double-blind trial of 137 individuals with ALS. These individuals were living independently, had an ALSFRS-R score of at least two points in each item, had normal respiratory function demonstrated by a forced vital capacity (FVC) greater than or equal to 80 percent, and had disease duration of two years or less. Over 90 percent of the individuals in this trial were taking riluzole concomitantly. The primary endpoint was the change in ALSFRS-R scores from baseline to 24 weeks, signifying a decrease in the rate of deterioration. The results of this trial showed a change in ALSFRS-R score of -5.01 in the edaravone (Radicava) group and -7.50 in the placebo group, indicating a statistically significant (p= 0.0013) difference between the treatment groups, favoring edaravone (Radicava).