Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Edaravone (Radicava™)

Policy #:08.01.42a

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, 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. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

EDARAVONE (RADICAVA)
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
  • Time from symptom onset is 2 years or less
  • Forced vital capacity (FVC) of ≥80%
  • Scores of 2 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.
Guidelines

BENEFIT APPLICATION

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

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. 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 (can't 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 degenerationby 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.

Revised El Escorial schema for the clinical diagnosis of amyotrophic lateral sclerosis (ALS)


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. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1:293.

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 3 to 5 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 6-month, randomized, placebo-controlled study in 205 Japanese individuals, with “definite” or “probable” ALS, with a duration of 3 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 group and -6.35 in the placebo group, demonstrating that the primary endpoint was not reached and, therefore, failed to establish efficacy of edaravone to delay the progression of ALS. A post hoc exploratory analysis was then done, and identified a subgroup of individuals in which edaravone may show effectiveness. This information was used to design another phase 3 clinical trial.

The second study was a 6-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 2 points in each item, had normal respiratory function demonstrated by a forced vital capacity (FVC) greater than or equal to 80%, and had disease duration of 2 years or less. Over 90% 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 group and -7.50 in the placebo group, indicating a statistically significant (p= 0.0013) difference between the treatment groups, favoring edaravone.
References


Abe K, Aoki M, Tsuji S, et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet.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). Drug Information 2017. Radicava. [Lexicomp Online Web site]. 03/22/2018. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 08, 2018.

Elman LB, McCluskey L. Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease. [UpToDate]. Updated 10/31/2018. Available at: https://www.uptodate.com/contents/diagnosis-of-amyotrophic-lateral-sclerosis-and-other-forms-of-motor-neuron-disease?search=Diagnosis%20of%20amyotrophic%20lateral%20sclerosis%20and%20other%20forms%20of%20motor%20neuron%20disease.&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 Accessed November 08, 2018.

Elman LB, McCluskey L. Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease. [UpToDate]. Updated 04/27/2018. Available at: https://www.uptodate.com/contents/diagnosis-of-amyotrophic-lateral-sclerosis-and-other-forms-of-motor-neuron-disease?search=Diagnosis%20of%20amyotrophic%20lateral%20sclerosis%20and%20other%20forms%20of%20motor%20neuron%20disease.&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 . Accessed November 08, 2018.

Elsevier’s Clinical Key.Amyotrophic lateral sclerosis. 11/06/2018 [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed November 08, 2018.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Radicava. 05/18/2017. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed November 08, 2018.

Lexi-Drugs Compendium. Radicava. 10/25/2018. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 08, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Radicava. 07/14/2017. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 08, 2018.

Radicava (edaravone). [prescribing information] Jersey City, NJ: Mitsubishi Tanabe Pharma Corporation; 2017. Issued 05/2017. Available at: https://www.radicava.com/assets/dist/pdfs/radicava-prescibing-information.pdf. Accessed November 08, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Radicava (edaravone) drug approval letter [FDA Web site]. 05/05/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed November 08 2018.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


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

Coding and Billing Requirements


Cross References


Policy History

Revisions for 08.01.42a
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS codes have been termed from this policy:
C9493 Injection, edaravone, 1 mg
J3490 Unclassified drugs

The following HCPCS code has been added to this policy:
J1301 Injection, edaravone, 1 mg

Revisions for 08.01.42
11/21/2018This policy has been reviewed and reissued to communicate the Company's continuing position on Edaravone (Radicava™).


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2019
Version Issued Date: 01/02/2019
Version Reissued Date: N/A

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