Radicava and Radicava ORS (edaravone) for amyotrophic lateral sclerosis

Last updated Jan. 24, 2024, by Teresa Carvalho, MS
Fact-checked by Ines Martins, PhD

What is Radicava for ALS?

Radicava (edaravone) is an approved infusion therapy used to slow functional decline in people with amyotrophic lateral sclerosis (ALS).

It now also is available as an oral formulation — called Radicava ORS in the U.S. and Radicava Oral Suspension in Canada — designed to offer the same efficacy as the intravenous (into-the-vein) formulation, while being more convenient.

Both formulations were developed by the Japanese company Mitsubishi Tanabe Pharma, and are marketed in the U.S. by its subsidiary Mitsubishi Tanabe Pharma America.

Therapy Snapshot

How does Radicava work?

ALS is a neurodegenerative disease characterized by the progressive damage and loss of motor neurons, the nerve cells responsible for voluntary movement. The causes of the disease are not fully understood, but one central mechanism that has been implicated in motor neuron death is oxidative stress.

Oxidative stress is commonly described as an imbalance between the production of toxic reactive molecules during normal cellular metabolism and the body’s ability to neutralize them with antioxidants. This imbalance leads to an increase in oxidative molecules that cause significant damage to cellular components.

While this can affect all cells, the neurons are particularly sensitive to oxidative stress. This happens because these cells have a very active metabolism, low antioxidant defenses, and a high content of molecules susceptible to oxidation.

Edaravone, the active ingredient in Radicava and Radicava ORS, is a free-radical scavenger, meaning it helps to remove the reactive molecules that can contribute to oxidative stress. By removing these toxic molecules and lowering oxidative stress, it is expected to reduce nerve damage and slow ALS progression.

Who can use Radicava?

Radicava was first approved for the treatment of ALS in Japan and South Korea in 2015. This was followed by approvals by the U.S. Food and Drug Administration (FDA) in 2017 — which made Radicava the first new ALS treatment available in the U.S. in more than 20 years. The therapy then was approved by Health Canada in 2018.

The FDA later extended its approval in 2022 to include an oral formulation of edaravone called Radicava ORS. A similar approval was granted in Canada later that year, where the oral formulation is known as Radicava Oral Suspension.

While none of the Radicava formulations are approved in the European Union, both the intravenous and oral formulations have been cleared for use in Switzerland.

Who should not use Radicava?

Both Radicava and Radicava ORS are not recommended for patients who experienced an allergic reaction to edaravone, sodium bisulfite, or any other component in the medications.

How is Radicava administered in ALS?

Radicava is delivered via intravenous (into-the-bloodstream) infusions, each lasting about one hour. These infusions contain 60 mg of the active medication and can be administered at multiple sites, including:

• an infusion center
• the doctor’s office
• a hospital
• the patient’s home.

Radicava ORS is an oral suspension available in a portable, amber, glass bottle. It is recommended at a dose of 105 mg, given with a 5 mL oral syringe, either orally or via a feeding tube.

The oral medication should be taken in the morning after overnight fasting, and patients are advised to ingest nothing but water for one hour after its administration. As it can be self-administered at home and doesn’t require traveling to an infusion center, the oral formulation has a greater convenience when compared with Radicava.

Both formulations follow the same dosing regimen, and are administered in 28-day cycles. In an initial treatment cycle, patients receive daily treatment for 14 consecutive days, followed by a two-week period without treatment. In subsequent cycles, the therapy is taken daily over 10 of the next 14 days, followed by two weeks of no treatment.

Radicava in clinical trials

Radicava’s approval in the U.S. was based on data from Study 19 (NCT01492686), a Japanese Phase 3 clinical trial that enrolled 137 people with ALS.

Study 19

Participants in Study 19 were randomly assigned to receive 60 mg of Radicava or a placebo for 24 weeks, or about six months.

The treatment schedule was similar to the now-approved regimen. In a first cycle, patients received treatment for 14 consecutive days, followed by two weeks without treatment. Subsequent cycles consisted of daily treatment for 10 of the following 14 days, followed by a two-week treatment-free period.

Trial results showed Radicava significantly slowed disease progression, as measured by changes in the ALS functional rating scale-revised (ALSFRS-R), by 33% compared with a placebo. After six months of treatment, those who received Radicava experienced an average decline of 5.01 points in their ALSFRS-R scores, while those on a placebo lost 7.5 points over the same period — a difference in decline of 2.49 ALSFRS-R points.

The medication also slowed disease progression on another validated scale, the Modified Norris Scale, and reduced quality of life deterioration. There also were fewer deaths in the Radicava group, although the difference failed to reach statistical significance.

Open-label extension

After completing the six-month trial, participants were given the option to enter an open-label extension part, in which all received Radicava for another 24 weeks. A total of 123 patients joined.

These findings showed that patients who were previously treated with Radicava continued to have slower disease progression, while patients who before had been a on the placebo started to benefit from the treatment.

A post-hoc analysis also demonstrated that if patients originally on a placebo had stayed on a placebo for the entire 48 weeks, they were expected to experience a decline reaching 13 ALSFRS-R points. This was significantly greater than the actual decline seen in Radicava-treated patients for 48 weeks, who experienced an 8-point reduction.

Radicava ORS in clinical trials

The approval of Radicava ORS was supported by Radicava’s efficacy data and pharmacological findings demonstrating that the oral formulation delivers similar amounts of the active medication to the body.

Phase 3 trial

Approval of the oral formulation also was supported by a global, MTPA-sponsored Phase 3 clinical trial (NCT04165824) that evaluated the safety and tolerability of Radicava ORS in 185 participants. All received a 105 mg dose of the oral medication, given in the approved treatment regimen for 48 weeks.

Radicava ORS was generally safe and well tolerated, and no treatment-related serious side effects were reported. Results also found a reduction in ALSFRS-R declines, meaning a slowing in disease progression, similar to that seen with the intravenous formulation.

Participants who completed the Phase 3 trial had the option to join a long-term extension study (NCT04577404). A total of 140 patients have chosen to enroll and are receiving Radicava ORS for up to 96 weeks.

Ongoing trials

Phase 3b trial of Radicava ORS

The safety and effectiveness of two dosing regimens of Radicava ORS — the approved regimen of 10 days on treatment and 18 days off versus once-daily dosing — against a placebo are being assessed in a Phase 3b clinical trial (NCT04569084) involving 384 adults with ALS.

Participants must have experienced their first ALS symptoms in the two years before their enrollment. Those assigned to Radicava ORS will all receive a 105 mg dose, regardless of their treatment regimen.

The trial’s main goal is to measure ALSFRS-R decline, while secondary assessments include changes in lung function, quality of life, and the time to needing ventilatory support, or death. Top-line data are expected in 2024.

Biomarker study

An observational trial (NCT04259255) called REFINE-ALS also is underway to identify biomarkers that could predict a person’s response to Radicava. A total of 300 patients are expected to enroll and be followed for about 24 weeks, which is six treatment cycles.

Common side effects of Radicava

The most common side effects associated with Radicava or Radicava ORS include:

• contusions, or bruises
• walking issues
• headache.

Allergic reactions

Radicava and Radicava ORS can cause allergic reactions, such as redness, swelling, and rash, and cases of anaphylaxis have been described in post-marketing studies.

Both the intravenous and oral formulations have sodium bisulfite in their composition, which may cause allergic reactions, including serious and life-threatening reactions. People with asthma are more frequently sensitive to bisulfite.

It is recommended people receiving edaravone-based medications are carefully monitored for these reactions, and treatment should be discontinued if they occur.

Pregnancy and breastfeeding

Based on animal studies, Radicava can cause harm to a developing fetus. It’s unknown if it can pass to breast milk in humans, but edaravone has been detected in the milk of lactating rats.

It is recommended patients who are pregnant or nursing, or plan to become pregnant or breastfeed, talk with their healthcare providers to know if it is safe for them and the baby to receive Radicava or Radicava ORS during those periods.

ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.