Medicare Advantage

Medical Policy

Title:

Edaravone (Radicava®)

Policy #:

MA08.092a

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Edaravone (Radicava) is considered medically necessary and, therefore, covered when all of the following criteria are met:

Diagnosis of definite or probable amyotrophic lateral sclerosis (ALS) per the revised El Escorial World Federation of Neurology criteria
Disease duration of two years or less
Forced vital capacity (FVC) of greater than or equal to 80 percent
Scores of two points or greater on each individual item of the ALS Functional Rating Scale-revised (ALSFRS-R)
Prescribed by or in consultation with a neurologist

EXPERIMENTAL/INVESTIGATIONAL

All other uses for edaravone (Radicava) are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).

Guidelines

There is no Medicare coverage determination addressing edaravone (Radicava); therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, edaravone (Radicava) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when edaravone (Radicava) is covered under a member's medical benefit (Part B benefit). It does not address instances when edaravone (Radicava) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Edaravone (Radicava) was approved by the FDA on May 5, 2017 for the treatment of individuals with amyotrophic lateral sclerosis (ALS). Edaravone (Radicava) is administered as an intravenous infusion over 60 minutes.

PEDIATRIC USE
The safety and effectiveness of edaravone (Radicava) in pediatric individuals have not been established.

ALS FUNCTIONAL RATING SCALE- REVISED (ALSFRS-R)

The ALSFRS-R scale is a series of 12 questions used by doctors to assess changes in physical functioning in individuals with ALS. The 12 questions are in the following categories: speech, salivation, swallowing, handwriting, cutting food, dressing and hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each question is graded from 0 (cannot do) to 4 (normal ability).

El ESCORIAL CRITERIA

El Escorial World Federation of Neurology criteria, also known as the Airlie House criteria, is the clinical standard for the diagnosis of ALS. Per this criteria, a diagnosis of ALS requires the presence of evidence of lower motor neuron degeneration by clinical, electrophysiologic, or neuropathological exam; evidence of upper motor neuron degeneration by clinical exam; and progressive spread of symptoms or signs within a region or to other regions as determined by history or exam. The four body regions are cranial, cervical, thoracic, and lumbosacral.

LMN: lower motor neuron signs (i.e., weakness, atrophy, fasciculations, dysarthria, dysphagia)

UMN: upper motor neuron signs (i.e., slowness of movement, incoordination, stiffness, poor dexterity, spastic gait with poor balance, dysarthria and dysphagia)

Brooks, BR, Miller, RG, Swash, M, Munsat TL. World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. ALS and Other Motor Neuron Disord. 2000;1:293-299.

Description

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that causes muscle weakness, disability, and death. It is caused by gradual degeneration and eventual death of the upper and lower motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and to the muscles throughout the body. Death of the motor neurons inhibits signals from the brain to the muscles, resulting in muscle atrophy. Eventually, the brain loses the ability to initiate and control voluntary movements.

The median survival of those diagnosed with ALS is three to five years, with most individuals succumbing to respiratory failure. There are approximately 7000 new cases in the United States diagnosed each year. ALS has been found to have a higher rate of occurrence in Caucasians, and has an average age of onset of 62 years.

Edaravone (Radicava) was approved by the US Food and Drug Administration on May 5, 2017 for the treatment of amyotrophic lateral sclerosis (ALS). The mechanism by which edaravone (Radicava) exerts its therapeutic effect is unknown; however, since it is classified as a free radical scavenger, it is thought to block radicals that mediate neuronal and vascular damage.

CLINICAL STUDIES

The efficacy of edaravone (Radicava) was studied in trials. The initial trial was a six-month, randomized, placebo-controlled study in 205 Japanese individuals, with “definite” or “probable” ALS, with a duration of three years or less, as determined by the revised El Escorial (Airlie House) criteria. Individuals were excluded if they had reduced respiratory function, complications that require hospitalization, or were undergoing cancer treatment. This trial consisted of a 12-week pre-observation period, followed by a 24-week treatment period. The primary endpoint was the change in ALSFRS-R (ALS Functional Rating Scale- revised) score. The mean change in ALSFRS-R score during treatment was -5.70 in the edaravone (Radicava) group and -6.35 in the placebo group, demonstrating that the primary endpoint was not reached and, therefore, failed to establish efficacy of edaravone (Radicava) to delay the progression of ALS. A post hoc exploratory analysis was then done, and identified a subgroup of individuals in which edaravone (Radicava) may show effectiveness. This information was used to design another phase three clinical trial.

The second study was a six-month, randomized, placebo-controlled, double-blind trial of 137 individuals with ALS. These individuals were living independently, had an ALSFRS-R score of at least two points in each item, had normal respiratory function demonstrated by a forced vital capacity (FVC) greater than or equal to 80 percent, and had disease duration of two years or less. Over 90 percent of the individuals in this trial were taking riluzole concomitantly. The primary endpoint was the change in ALSFRS-R scores from baseline to 24 weeks, signifying a decrease in the rate of deterioration. The results of this trial showed a change in ALSFRS-R score of -5.01 in the edaravone (Radicava) group and -7.50 in the placebo group, indicating a statistically significant (p= 0.0013) difference between the treatment groups, favoring edaravone (Radicava).

References

Abe K, Aoki M, Tsuji S, et al. Safety and efficacy of edaravone in well-defined patients with amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial. The Lancet Neurol. 2017;16(7):505-512.

Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(7-8):610-617.

American Hospital Formulary Service (AHFS). Edaravone (Radicava®). Drug Information 2021. [Lexicomp Online Web site]. 02/26/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 19, 2021.

Brooks BR, Miller RG, Swash M, Munsat TL. World Federation of Neurology Research Group on motor neuron diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. ALS and Other Motor Neuron Disord. 2000;1:293-299.

Edaravone (Radicava®). Prescribing information. Jersey City, NJ: Mitsubishi Tanabe Pharma Corporation. 03/2021. Available at: https://www.radicava.com/assets/dist/pdfs/radicava-prescibing-information.pdf. Accessed April 19, 2021.

Elman LB, McCluskey L. Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease. [UpToDateWeb site]. 11/09/2020. Available at: https://www.uptodate.com/contents/diagnosis-of-amyotrophic-lateral-sclerosis-and-other-forms-of-motor-neuron-disease?search=Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease.&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [via subscription only]. Accessed April 19, 2021.

Elman LB, McCluskey L. Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease. [UpToDate web site]. 02/11/2021. Available at: https://www.uptodate.com/contents/clinical-features-of-amyotrophic-lateral-sclerosis-and-other-forms-of-motor-neuron-disease?search=Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [via subscription only]. Accessed April 19, 2021.

Elsevier’s Clinical Key. Amyotrophic lateral sclerosis. Clinical overview. [Clinical Key Web site]. 02/26/2021. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 19, 2021.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Edaravone (Radicava®). [Clinical Key Web site]. 03/18/2021. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 19, 2021.

IBM Micromedex® DRUGDEX® (electronic version). Edaravone (Radicava®). [Micromedex Web site]. IBM Watson Health, Greenwood Village, Colorado, USA. 03/23/2021. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 19, 2021.

Lexi-Drugs Compendium. Edaravone (Radicava®). [Lexicomp Online Web site]. 03/29/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 19, 2021.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Edaravone (Radicava®). [FDA Web site]. 03/15/2021. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed Accessed April 19, 2021.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Edaravone (Radicava®). Premarket approval letter. [FDA Web site]. 05/05/2017. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/209176Orig1s000ltr.pdf. Accessed April 19, 2021.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

G12.21 Amyotrophic lateral sclerosis

HCPCS Level II Code Number(s)

J1301 Injection, edaravone, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Version Effective Date:

12/28/2018

Version Issued Date:

12/30/2018

Version Reissued Date:

6/1/2022