Clinical Policy: Edaravone (Radicava, Radivaca ORS) Form

Clinical Policy: Edaravone (Radicava, Radivaca ORS)
Reference Number: CP.PHAR.343
Effective Date: 07.01.17
Last Review Date: 05.26
Line of Business: Commercial, HIM/ICHRA, Medicaid

[Coding Implications](Coding Implications)
[Revision Log](Revision Log)

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.

Description
Edaravone (Radicava®, Radicava ORS®) is a member of the substituted 2-pyrazolin-5-one class that acts as a free-radical scavenger of peroxyl radicals and peroxynitrite.

FDA Approved Indication(s)
Radicava and Radicava ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS).

Policy/Criteria

a. One of the following (i or ii):  
    i. For intravenous administration: 60 mg per day for each treatment cycle;  
    ii. For oral administration: 105 mg per day for each treatment cycle;  
b. For initial treatment cycle: daily dosing for 14 days followed by a 14-day drug-free period;  
c. For subsequent treatment cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods.

Approval duration:
Medicaid/HIM/ICHRA – 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

II. Continued Therapy
A. Amyotrophic Lateral Sclerosis (must meet all):

a. Either of the following (i or ii):  
    i. For intravenous administration: 60 mg per day for each treatment cycle;  
    ii. For oral administration: 105 mg per day for each treatment cycle;  
b. Treatment cycle consisting of daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods.

Approval duration:
Medicaid/HIM/ICHRA – 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Other diagnoses/indications (1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:
A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV. Appendices/General Information
Appendix A: Abbreviation/Acronym Key
ALS: amyotrophic lateral sclerosis
FVC: forced vital capacity
ALSFRS-F: revised ALS Functional Rating Scale
LMN: lower motor neuron
UMN: upper motor neuron
FDA: Food and Drug Administration

Appendix B: Therapeutic Alternatives
This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic.

Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): hypersensitivity to edaravone or any of the inactive ingredients in Radicava and/or Radicava ORS
• Boxed warning(s): none reported

Appendix D: General Information

• Revised El Escorial/Airlie House diagnostic criteria for ALS requires the presence of:
  
  1. Signs of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination,
  2. Signs of upper motor neuron (UMN) degeneration by clinical examination, and
  3. Progressive spread of symptoms or signs within a region or to other regions, together with the absence of:
     a. Electrophysiological evidence of other disease processes that might explain the signs of LMN and/or UMN degenerations; and
     b. Neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs.
• The definitions of ALS diagnoses provided by the revised El Escorial/Airlie House criteria are as follows:

• Two pivotal phase III trials that were conducted in Japan were used for the approval of Radicava in the USA. One of the phase III trials of Radicava found no statistically significant difference in delay of ALS progression, but a post-hoc analysis found that a certain subset of patients may benefit. Based on the post-hoc analysis, the second phase III was performed with a much more strict eligibility criteria and found a statistically significant difference in ALS progression in favor of Radicava. Therefore, patients not meeting the strict eligibility criteria at any time (at the time of initial or continued approval) can be assumed that no benefit will be provided by the use of Radicava for the treatment of ALS until further studies support its use in a wider population with ALS.
• The revised ALS Functional Rating Scale (ALSFRS-R) score consists of a total of 12 items and 48 points. It is a physician-generated estimate of the patient’s degree of functional impairment. Each item assesses the patient’s functional ability on daily tasks, such as walking and hand-writing. Each item is scored from 0 to 4 points, with 0 indicating no ability and 4 indicating normal ability.

V. Dosage and Administration

VI. Product Availability

VII. References

1. Radicava Prescribing Information. Jersey City, NJ: MT Pharma America, Inc.; December 2025. Available at: https://www.radicava.com. Accessed January 12, 2026.
2. The Writing Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2017; S1474-4422(17)30115-1.
3. 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. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2014;15(7-8), 610-617.
4. Yoshino H and Kimura A. Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study). Amyotrophic Lateral Sclerosis. 2006;7(4), 247-251.
5. Brooks BR, Miller RG, Swash M, et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9.
6. Anderson PM, Borasio GD, Dengler R, et al. Good practice in the management of amyotrophic lateral sclerosis: Clinical guidelines. An evidence-based review with good practice points. EALSC Working Group. Amyotrophic Lateral Sclerosis. 2007, 8:195-231.
7. Hardiman O, van den Berg LH, and Kiernan MC. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nature Reviews Neurology 2011; 7: 639-649. doi:10.1038/nrneurol.2011.153
8. Takei K, Tsuda K, Takahashi F, et al. An assessment of treatment guidelines, clinical practices, demographics, and progression of disease among patients with amyotrophic lateral sclerosis in Japan, the United States, and Europe. Amyotroph Lateral Scler Frontotemporal Degener 2017; 18: 88–97. DOI: 10.1080/21678421.2017.1361445.
9. Shoesmith C, Abrahao A, Benstead T, et al. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ. 2020 Nov;192(46):E1453-E1468.
10. Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13 (reaffirmed February 2023);73(15):1218-26.
11. Van Damme P, Al-Chalabi A, Andersen PM, et al. European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD). Eur J Neurol. 2024;31(6):e16264.

Coding Implications
Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

Reviews, Revisions, and Approvals

Important Reminder
This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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