Radicava/Edaravone

Background

Edaravone is a drug sold under the names, Radicava or Radicut. Japan, South Korea, Canada, Switzerland, China, Indonesia, Thailand, Malaysia, Brazil and the United States have approved its use to treat people with Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease (MND).

Intravenous (IV) edaravone (Radicut) has been used in Japan since 2001 for the acute treatment of neurological symptoms related to ischemic stroke. Based on its proposed mechanism of action, a Japanese clinician suggested edaravone may be effective in treating ALS/MND. This led Mitsubishi Tanabe Pharma America, the owners of Radicut, to examine this possibility in clinical trials.

Approved in:	Commercial Name:
Australia	Radicava®
Brazil	Radicava®
Canada	Radicava® injection 30 mg/100 mL
Canada	Radicava Oral Suspension (ORS)
Japan	Radicut® bag 30 mg/100 mL Radicut® ampule 30 mg/20 mL
Japan	RADICUT® Oral Suspension 2.1%
Indonesia	Radicava® IV concentrate solution for infusion 30 mg/20 mL
Malaysia	Radicava® IV concentrate solution for infusion 30 mg/20 mL
South Korea	Radicut® ampule 30 mg/20 mL
Switzerland	Radicava® 30 mg/100 mL
Switzerland	Radicava® oral suspension
Thailand	Radicava®
USA	Radicava® 30 mg/100 mL
USA	Radicava Oral Suspension (ORS)

Proposed Mechanism of Action

Several studies have shown that edaravone may act as a free-radical scavenger (or antioxidant) and may protect cells from damage inflicted by oxidative stress, which is hypothesized to be one of the mechanisms causing neuronal toxicity in ALS/MND. Currently it remains unclear how edaravone may have an effect in ALS/MND and studies are ongoing. All other clinical trials using antioxidant compounds have been ineffective for treating ALS/MND to date.

Edaravone IV in Clinical Trials

Multiple clinical trials of edaravone (Radicut) in ALS/MND were conducted in Japan for more than a decade. An initial double-blind, placebo-controlled study (MC-186) demonstrated a trend towards benefit for those treated with edaravone, but this was not statistically significant. Follow up (post-hoc) analysis revealed that a subgroup of participants earlier in the disease appeared to benefit compared to those further progressed. A second double-blind, placebo-controlled clinical trial was conducted, enrolling only individuals with the earlier disease criteria observed to benefit in the previous study and a statistically significant benefit was observed, with a difference of 2.49 ALSFRS-r points between the active treatment and placebo groups over 24 weeks. These results led to approval of edaravone in several countries, notably by the United States FDA in 2017 as Radicava.

Since approval of IV Radicava, MT Pharma has created an oral suspension formulation, which was approved by the FDA as Radicava ORS and Health Canada as Radicava Oral Suspension in 2022. Further clinical trials demonstrated that the oral edaravone acts in an equivalent manner in the body, is safe and is well tolerated.

Another oral formulation of edaravone, TW001, was created by the company Treeway in The Netherlands. TW001, also called FAB122, was tested in a double-blind, placebo-controlled Phase 3 clinical trial across Europe, called the ADORE study, that did not demonstrate benefit versus placebo. It is unknown how comparable this form of edaravone is to the MT Pharma drug and more details are expected later in 2024. More information about the oral formulation of Radicava can be found here.

Dose and Administration

Administration of edaravone occurs as a 28-day cycle. Edaravone is administered via IV infusion of 60 mg over 60 minutes once daily for 14 days followed by 14-days of a treatment-free period, after which the cycle repeats with a change to edaravone only on 10 out of 14 days during the treatment period. RADICAVA ORS uses the same dosing regimen as RADICAVA IV and is administered orally via mouth or feeding tube with a 5mL syringe.

Reported Side Effects

Edaravone is generally safe and well tolerated at the recommended dose. Commonly reported adverse effects of edaravone IV administration include issues walking, bruising, headaches, fatigue, and constipation. Serious adverse events reported from these studies include respiratory disorders, dysphagia, pneumonia aspiration, and musculoskeletal disorders.

Edaravone should be administered and monitored under the care of a physician.

Current Status

Our understanding of edaravone as a treatment for ALS/MND is constantly evolving. There are conflicting results with some studies suggesting a small benefit while other studies show no benefit. As more information arises, the Alliance will attempt to keep this document updated with current learnings.

Disclaimer: Consult with your doctor to determine if edaravone/Radicava is an option for you. Always disclose your medical history, including any drugs, natural supplements, or herbal medicines currently being used. Your doctor will determine the right plan for your needs.

SOURCES

International Alliance of ALS/MND Associations
September 2024

The original language of communication is English and any translation cannot be guaranteed for accuracy of messaging.