Long-term Radicava Safe, Modestly Effective in Small Korean Study
Modest improvement was observed in patients with advanced ALS
Long-term use of Radicava (edaravone) is safe and may modestly slow disease progression in people with amyotrophic lateral sclerosis (ALS), according to a small Korean study.
Patients also experienced no changes in phrenic nerve function, which is required for the contraction and expansion of the diaphragm muscle.
“Further well-designed studies are warranted to clarify the effect of edaravone and its possible adverse events after extended therapy,” the study authors wrote.
The study, “Long-term outcomes of edaravone in amyotrophic lateral sclerosis in South Korea: 72-week observational study,” was published in BMC Neurology.
Radicava, developed by Mitsubishi Tanabe Pharma, was approved for ALS in Japan and South Korea in 2015 and in the U.S. in 2017. Administered via into-the-vein infusions, the medication works by reducing oxidative stress, a type of cellular damage that has been implicated in ALS.
The approvals were based on data from a Phase 3 trial called Study 19 (NCT01492686), which enrolled 137 ALS patients with a maximum disease duration of two years. In this trial, six months of treatment slowed functional decline — as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R) — by 33% compared with a placebo.
However, recent real-world studies in Italy and Germany have found no differences in disease progression or respiratory function. Also, researchers are concerned that the inclusion of patients with early ALS in Study 19 may prevent the generalization of benefits to populations with longer disease duration.
To address this, a research team in South Korea conducted an observational study to determine the long-term safety and efficacy of Radicava among patients who received the treatment at their clinic from December 2015 to May 2021.
Radicava is administered in 28-day cycles. In the first cycle, patients receive the therapy over 14 consecutive days, which are followed by two weeks without treatment. In the following cycles, infusions are given over 10 of the first 14 days, also followed by two weeks off treatment.
A total of 50 patients received at least one Radicava injection during the follow-up period. Among them, 30 completed six cycles of Radicava and 16 agreed to continue receiving an extended treatment regimen after those six cycles.
These 16 patients included 10 men and six women, with a mean age of 58.3 years. The median time from symptom onset to an ALS diagnosis was 14.5 months, and it took a median of 8.1 months from diagnosis to their first Radicava infusion.
Eleven of these patients underwent more than 18 cycles of treatment and were assessed up to 72 weeks (about 1.5 years).
What were the results of the long-term Radicava study?
Results showed that ALSFRS-R scores declined on average 0.81 points per month over the 72-week period. This decline, however, was not linear over time, with patients losing on average 0.96 points per month in the first 24 weeks, 0.7 points per month between weeks 24 and 48, and 1.18 monthly points between weeks 48 and 72.
The forced vital capacity test, a measure of how much air can be forcibly exhaled from the lungs in one breath, was used to monitor lung function. In these patients, the mean score declined significantly from 90.5 at the study’s start to 72.3 at follow-up.
However, the activity of the phrenic nerve, which controls diaphragm muscle movement, was not significantly changed after treatment.
Statistical analyses then demonstrated that albumin levels at the start of the study could be used to predict ALSFRS-R scores after 24 weeks. Creatinine, a normal waste product from muscle metabolism, at 24 weeks correlated with ALSFRS-R scores at the study’s start, at 24 weeks, and at 72 weeks.
Creatinine at 72 weeks was also linked to ALSFRS-R scores at 72 weeks and to the change in ALSFRS-R scores from the study’s start to 72 weeks.
No patients experienced significant adverse events that led to treatment discontinuation. Common side effects included constipation, insomnia, headache, and transient low white blood cell counts.
Six patients required a tracheostomy to insert a breathing tube during the study and nine needed a feeding tube. One patient died after 36 weeks of treatment due to recurrent aspiration pneumonia, which occurs when food enters the airways instead of being swallowed.
“Our results show that long-term treatment with edaravone was well tolerated with no significant adverse events that led to the discontinuation of the treatment. Moreover, modest improvement was observed in advanced ALS patients,” the researchers wrote. “Thus, a 72-week treatment with edaravone can be considered safe with modest improvement.”
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