Radicava’s Real-world Safety Profile Matches Clinical Trial Data: Study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Using the approved treatment Radicava (edaravone) in a real-world setting resulted in a similar safety profile as that reported in clinical trials, with no new safety signals identified, according to a new report.

The analysis involved more than 5,000 people with amyotrophic lateral sclerosis (ALS) who received the medication during the three years after its approval.

The study, “Analysis of the US Safety Data for Edaravone (Radicava) From the Third Year After Launch,” was published in Drugs in R&D. It was funded and conducted by Mitsubishi Tanabe Pharma America (MTPA), which markets Radicava in the U.S.

“We are pleased to share three-year findings from the post-marketing safety analysis of Radicava that reinforce its well-established safety profile as reported in clinical trials,” Gustavo A. Suarez Zambrano, MD, vice president of medical affairs at MTPA, said in a company press release.

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“We remain focused on learning as much as possible about the use of Radicava in a real-world setting, and these data signify an additional milestone toward achieving that goal,” Suarez said.

Radicava was approved by the U.S. Food and Drug Administration in 2017 for treating ALS. Administered by infusions into the bloodstream, the medication works by reducing a type of cell damage called oxidative stress, which contributes to nerve cell death in ALS.

In Study 19 (NCT01492686), the Japan-based Phase 3 clinical trial that led to Radicava’s approval in the U.S. and other countries, the most common side effects of the medication were walking problems, bruises, and headaches.

Scientists at MTPA and other institutions examined the safety outcomes of ALS patients who received Radicava in the U.S. in a real-world setting. The report included data collected as part of post-marketing surveillance by MTPA, as well as from a prescription data aggregator. The scientists emphasized that the analysis carries inherent limitations since the data was voluntarily reported.

“Because all the registrational clinical studies for [Radicava] were conducted in Japan, there is considerable interest in how this drug is being utilized in clinical practice in the United States and, in particular, its safety in the real-world setting,” the team wrote.

A total of 5,207 ALS patients were treated with Radicava in the U.S. between 2017 and 2020. Of the 3,152 patients with available safety reports, 6,235 safety-related events were reported, 1,583 of which were deemed serious.

The most common adverse events were: death (whose cause was not specified), the drug was ineffective, disease progression, unexpected changes in symptom severity, fall, lack of energy, fatigue, muscle weakness, walking difficulty, and shortness of breath.

The majority of these events were likely attributable to the underlying disease, the researchers said. In fact, “because [Radicava] is not a cure, nor expected to reverse the disease process, these aforementioned [adverse events] are anticipated in a pharmacovigilance program,” the team wrote.

The scientists highlighted five cases of severe anaphylaxis (an acute allergic reaction), which manifested as trouble breathing or swallowing, itching, and swelling. “Anaphylactic reactions were not seen in the randomized controlled ALS trials that were conducted in Japan,” they wrote.

They speculated that the allergic reaction may be caused by a stabilizing agent in the therapy called bisulfite. People with asthma or chronic urticaria are particularly likely to be sensitive to this agent.

Notably, vitamin B12 supplements are often administered to people with ALS in Japan — and this vitamin also has been shown to reduce the severity of bisulfite reactions.

“We recommend evaluating ALS patients for asthma as well as chronic urticaria and assessing their need for vitamin B12 supplementation that might mitigate allergic and anaphylactic responses to sulfites,” the research team wrote.

The researchers also highlighted 95 side effects related to the therapy’s infusion, including 34 infections in the infusion site or equipment. Of these infections, 22 were serious, though none were fatal.

The overall rate of infusion-related infections was generally lower than what would be expected based on data from ALS patients given placebo infusions in clinical trials, they noted. “Infectious complications of the central venous catheter delivery systems were noted but at apparently reduced rates compared with literature reports,” the researchers wrote.

Overall, the analysis did not reveal any safety signals that were not already detected in clinical trials of Radicava, the researchers concluded.

“I am encouraged to see that the safety and tolerability profile of Radicava observed over the three-year post-marketing treatment period is consistent with reports from the clinical trials. These data provide [healthcare practitioners] with additional insights they can share with patients when considering treatment with Radicava,” Benjamin Rix Brooks, MD, an ALS specialist and study co-author, said.