Coverage Policy Manual
Policy #: 2017026
Category: Pharmacy
Initiated: July 2017
Last Review: August 2018
  Edaravone

Description:
Edaravone is a free radical scavenger/antioxidant approved for the treatment of amyotrophic lateral scleorosis (ALS). It has been previously investigated for the treatment of ischemic stroke, reperfusion Injury, and myocardial Infarction as it possesses antioxidant and anti-apoptotic properties. Being a low molecular weight molecule with good water and lipid-soluble properties, These are potential therapeutic advantages in crossing the blood-brain barrier to mediate nootropic and neuroprotective effects.
 
Researchers first developed the free radical scavenger edaravone in late 1980s as a treatment for stroke. The approach aimed to prevent the swelling of the brain which may occur after a stroke. It has been marketed in Japan by Mitsubishi Pharma for stroke since 2001 and is now generic.
 
Earlier trials of the drug in patients with all stages of ALS did not demonstrate a benefit.
 
Regulatory
Radicava™ was FDA approved for the treatment of amyotrophic lateral sclerosis (ALS) in May 2017.
 
 
Coding
Effective January 01, 2019, there is a specific HCPCS code for Edaravone.

Policy/
Coverage:
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
 
The initial use of edaravone in the treatment of amyotrophic lateral sclerosis (ALS) meets primary coverage criteria and is covered for members with contracts without primary coverage criteria when all of the following criteria are met:
 
    1. A diagnosis of definite or probable ALS according to the revised El Escorial criteria of signs of lower motor neuron degeneration and upper motor neuron degeneration in at least 2 topographical regions of the CNS based on the submission of medical records (chart notes, previous medical history, diagnostic testing including: imaging, nerve conduction studies, laboratory values) and seen either primarily or in consultation by a neurologist with expertise in the diagnosis and treatment of ALS,  AND
    2. Age 18 to 75, AND
    3. Functionality retained most activities of daily living (defined as scores of 2 points or better on each individual item of the ALS Functional Rating Scale – Revised [ALSFRS-R; described below]), AND
    4. Forced vital capacity greater than or equal to 80%, AND
    5. Disease duration of less than or equal to 2 years, AND
    6. Dosing regimen is consistent with FDA labeling:
        1. 60mg daily for 14 days, followed by a 14 day drug-free period as the initial treatment cycle administered IV
        2. then 60mg daily for 10 out of 14 days, followed by a 14 day-drug free period for all subsequent cycles administered IV.
 
Initial authorization is for 180 days with a limit of <74 doses.
 
Continuation of therapy will require evidence that the member is not dependent on invasive ventilation and will be for 180 days with a limit of 70 doses.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of edaravone for all other indications in the treatment of ALS and for all other conditions (including but not limited to stoke, MI, other neurodegenerative disease) does not meet primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of edaravone for all other indications in the treatment of ALS and for all other conditions (including but not limited to stoke, MI, other neurodegenerative disease) is considered investigational.

Rationale:
Edaravone was evaluated in a phase III study in patients with ALS and did not show a significant difference in the Revised ALS Functional Rating Scale as compared with placebo.  A post-hoc analysis showed that a subset of patients with ALS in the early stage showed a greater effect than the entire study population.  A phase III, randomized, double-blind, parallel-group study was then conducted to confirm the effect on this population subset.  A total of 213 patients were screened and 192 were enrolled as potential participants.  Eligible patients were aged 20 to 75 with definite or probable ALS according to the El Escorial criteria and had grade 1 or 2 ALS according to the Japan ALS Severity Classification, a forced vital capacity of greater than or equal to 80%, and disease duration of two years or less.  Inclusion criteria also required scores of at least 2 points on all 12 items of the Revised ALS Functional Rating Scale and that the patient had a decrease of 1 to 4 points in the Revised ALS Functional Rating Scale score during the 12-week observation period before randomization.  Of the 192 potential participants, 137 completed the observation and were randomized to either edaravone or placebo at a dose of 60mg daily for 14 days, followed by a 14 day drug-free period as the initial treatment cycle, followed by 60mg daily for 10 out of 14 days, followed by a 14 day-drug free period for subsequent cycles.  The primary endpoint was the change in the Revised ALS Functional Rating Scale score from baseline to week 24.  The mean change from baseline in the score in the edaravone group was -5.01 compared with -7.50 (p=0.0013). More patients discontinued treatment in the placebo group as compared to the treatment group (8 vs 2).3
 
Revised ALS Functional Rating Scale
 
The ALSFRS-R scale consists of 12 questions that evaluate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS (speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency). Each item is scored from 0-4, with higher scores representing greater functional ability.
 
The Revised Functional ALS Rating Scale is a validated questionnaire-based scale that measures physical function in carrying out activities of daily living in 12 domains with the following scoring system:
 
Speech: Scale  4: Normal speech processes, 3: Detectable speech disturbance, 2: Intelligible with repeating, 1: Speech combined with nonvocal communication, 0: Loss of useful speech
 
Salivation:
Scale 4: Normal, 3: Slight but definite excess of saliva in mouth; may have nighttime drooling, 2:  Moderately excessive saliva; may have minimal drooling, 1:  Marked excess of saliva with some drooling, 0: Marked drooling; requires constant tissue or handkerchief
 
Swallowing:  
Scale  4:  Normal eating habits, 3: Early eating problems – occasional choking, 2: Dietary consistency changes, 1: Needs supplemental feeding tube, 0:  NPO (exclusively parenteral/enteral feeding)
 
Handwriting:
Scale  4: Normal, 3: Slow or sloppy:  all words are legible, 2:  Not all words are legible, 1:  Able to grip pen but unable to write, 0: Unable to grip pen
 
Cutting Food & Handling Utensils
Scale:
Patients without Gastronomy   4: Normal, 3: Somewhat slow and clumsy but no help needed, 2: Can cut most foods, although clumsy and slow; some help needed, 1: Food must be cut by someone, but can still feed slowly, 0: Needs to be fed
 
 Patients with Gastronomy 4: Normal, 3: Clumsy but able to perform all manipulations independently, 2: Some help needed with closures and fasteners, 1: Provides minimal assistance to caregiver, 0: Unable to perform any aspect of task
 
Dressing & Hygiene
Scale 4: Normal function, 3: Independent and complete self-care with effort or decreased efficiency, 2: Intermittent assistance or substitute methods, 1: Needs attendant for self-care, 0: Total dependence
 
Turning in bed & Adjusting Bed Clothes
Scale
4: Normal, 3: Somewhat slow and clumsy, but no help needed, 2: Can turn alone or adjust sheets, but with great difficulty, 1: Can initiate, but not turn or adjust sheets alone, 0: Helpless
 
Walking:
Scale  4: Normal,3: Early ambulation difficulties, 2: Walks with assistance, 1: Nonambulatory functional movement, 0: No purposeful leg movement
 
Climbing:
Scale 4: Normal, 3: Slow, 2: Mild unsteadiness or fatigue, 1:  Needs assistance, 0: Cannot do
 
Dyspnea:
Scale 4:  None, 3: Occurs when walking, 2: Occurs with one or more of the following:  eating, bathing, dressing (ADL), 1: Occurs at rest, difficulty breathing when either sitting or lying, 0: Significant difficulty, considering using mechanical respiratory support
 
Orthopnea:
Scale 4: None, 3: Some difficulty sleeping at night due to shortness of breath; does not routinely use more than two pillows, 2: Needs extra pillows in order to sleep (more than two), 1:  Can only sleep sitting up, 0: Unable to sleep
 
Respiratory Insufficiency
Scale  4: None, 3: Intermittent use of BiPAP, 2: Continuous use of BiPAP during the night, 1: Continuous use of BiPAP during the night and day, 0: Invasive mechanical ventilation by intubation and tracheostomy
 
2018 Update
A literature search conducted using the MEDLINE database did not reveal any new
literature that would prompt a change in the coverage statement.

CPT/HCPCS:
C9493Injection, edaravone, 1 mg
J1301Injection, edaravone, 1 mg
J3490Unclassified drugs
J3590Unclassified biologics

References: Abe K, Itoyama Y, Sobue G, et al.(2014) Edaravone ALS Study Group. 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 Dec;15(7-8):610-7. doi: 10.3109/21678421.2014.959024. Epub 2014 Oct 6.

Abe, KojiAbe, Koji et al.(2017) Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017

Cedarbaum JM, Stambler N, Malta E, et al.(1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999;169(1-2):13-21.

Edaravone. Clinical Pharmacology [Internet]. Edaravone. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. c2017- [cited 2017 June 19]. Available from: http://www.clinicalpharmacology.com

Radicava® [package insert]. Jersey City, NJ: MT Pharma America, Inc.,2017


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.