Radicava Seen in Real-world Study to Prolong Survival With ALS
More patients on Radicava in US database study alive 2.5 years out than others
Real-world use of Radicava (edaravone) significantly prolongs survival in amyotrophic lateral sclerosis (ALS) patients, with people in the U.S. on the therapy living about six months longer than those not on this treatment, an analysis of Radicava’s use in clinical settings reported.
The estimated probability of survival was greater for Radicava-treated patients across several timepoints. At 30 months or 2.5 years, almost 50% of these patients were estimated to be alive compared with 42.6% of non-users.
“Real-world data may bridge gaps in knowledge that exist between clinical trials and everyday medical practice,” Gustavo Suarez Zambrano, MD, vice president of medical affairs at Mitsubishi Tanabe Pharma America (MPTA), which markets Radicava in the U.S., said in a company press release.
“While a randomized clinical trial is required to support the findings from this analysis, these data provide important insights from a real-life setting and deepen our understanding of Radicava’s role in the treatment of ALS,” Zambrano added.
The study, “Intravenous edaravone treatment in ALS and survival: an exploratory, retrospective, administrative claims analysis,” was published in eClinicalMedicine. MPTA funded this study, and its employees were among its researchers.
Infused directly into the bloodstream or taken as an oral suspension, Radicava works to decrease oxidative stress, a type of cellular damage thought to contribute to nerve cell death in ALS. Approved in Japan and South Korea in 2015, Radicava in 2017 became the first new ALS therapy in 2o years to be made available to U.S. patients. A potentially more convenient oral suspension formulation, called Radicava ORS, was given FDA approval in May.
Radicava shown in Phase 3 trial to slow decline
These approvals were largely based on data from a Phase 3 trial, called Study 19 (NCT01492686), which enrolled 137 adults with ALS in Japan. Top-line data from the six-month, randomized trial showed that Radicava as an infusion treatment significantly slowed functional decline by 33% compared with patients on a placebo.
In a subsequent trial extension, all participants were given Radicava for an additional six months. Findings showed that those treated since the start of Study 19 continued to show slower disease progression, and those who switched from placebo started to experience similar benefits.
Further analyses spanning the Phase 3 trial and its extension also showed that patients initially randomized to Radicava had a 53% lower cumulative risk of death, permanent assisted ventilation, or a tracheostomy, compared with those who started the therapy six months later.
Tracheostomy is a surgical procedure to create an opening in the windpipe for a breathing tube.
Contrasting with clinical trial data, Radicava studies in real-world settings have reported variable effects of the treatment. For this reason, MPTA set out to evaluate the real-life survival rates of ALS patients using Radicava, and compare these rates with a control group of patients who never used the treatment.
“Long-term survival was not assessed” in the Phase 3 clinical trial “because of limited study duration,” the researchers noted.
Patient data came from the Optum’s Clinformatics Data Mart, a de-identified database containing administrative health claims for people in the U.S. with commercial and Medicare Advantage health insurance plans.
Data covered 320 diagnosed ALS patients using Radicava between Aug. 8, 2017, and March 31, 2020, and 12,572 others who never received the medication. Some in this patient group may have been using riluzole (marketed as Rilutek, among other brand names), also approved to slow ALS progression; the study noted that “in both groups, 208 patients (65.4%) had a history of riluzole prescription.”
To ensure that patients and controls were well matched, the team then used a process called propensity scoring.
Essentially, this matches each Radicava patient with a control patient of the same sex, age, race, geographical region, insurance type, co-existing conditions, medication history, and a range of clinical measures relating to ALS disease duration, severity, and progression.
Ultimately, the analysis included 318 adult ALS patients given the therapy and 318 matched controls. The mean age in both groups was about 63, and most patients were male and white.
Patients overall had started Radicava about seven months after their diagnosis, and treatment continued for a median of 8.6 months.
As of March 31, 2021, fewer Radicava-group patients died from any cause compared with those not using the medication. Specifically, 155 deaths (48.7%) were reported among treated patients and 196 (61.6%) among controls.
27% overall lower risk of death with Radicava seen
Median survival time was 29.5 months with Radicava and 23.5 months without it, amounting to a 27% overall lower risk of death.
Further analyses estimated the number of patients alive at each time point. After one year, the estimated probability of survival was 83.7% for those treated with Radicava and 70.4% for those who were not.
After 18, 24, and 30 months, estimated survival probability in treated individuals was 68.5%, 59.1%, and 49.9%, respectively. By comparison, probability rates were 58.7%, 49%, and 42.6% among those not using Radicava for those timepoints.
Findings overall suggest that Radicava could improve survival in real-world settings.
“ALS has been a clinically challenging disease to evaluate due to its heterogeneity and average life expectancy,” said Benjamin Rix Brooks, MD, with the University of North Carolina School of Medicine–Charlotte Campus, and the study’s lead author.
“The results from this analysis showed that, for this specific group, treatment with Radicava led to the observation of a lower number of deaths and risk of death as well as longer overall survival estimates compared to those not on therapy,” he added. “These real-world findings are encouraging and will help inform future research for this devastating disease.”
The researchers concluded: “These findings, in a larger, more diverse group of treated patients with ALS compared with those who were included in the original [clinical trials], are promising for the hypothesis that beneficial [Radicava] treatment effects on rate of functional change in short-term … may be translated into increased survival, which should be tested in an adequately powered” and randomized clinical trial.