Last Review Date: 01/06/2025

Date of Origin: 12/12/2017

Dates Reviewed: 12/2017, 03/2018, 06/2018, 10/2018, 11/2019, 01/2020, 10/2020, 03/2021, 08/2021, 10/2022, 10/2023, 05/2024, 10/2024, 01/2025

1. Length of Authorization

• Initial: 6 months for severe eosinophilic asthma; 12 months for EGPA and all other indications
• Renewal: 12 months for all indications

2. Dosing Limits

    Max Units (per dose and over time) [HCPCS Unit]:

2. Severe Eosinophilic Asthma
   • Load: 30 billable units every 28 days for 3 doses
   • Maintenance: 30 billable units every 56 days
3. Eosinophilic Granulomatosis with Polyangiitis (EGPA)
   • 30 billable units every 28 days
4. Initial Approval Criteria

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR

B. BOTH of the following:

1. ONE of the following:
   1. The patient has a diagnosis of severe eosinophilic asthma and ALL of the following:
      1. The patient’s diagnosis has been confirmed by ONE of the following:
         1. The patient has a baseline (prior to therapy with the requested agent) blood eosinophil count of 150 cells/microliter or higher while on high-dose inhaled corticosteroids or daily oral corticosteroids OR
         2. The patient has a fraction of exhaled nitric oxide (FeNO) of 20 parts per billion or higher while on high-dose inhaled corticosteroids or daily oral corticosteroids OR
         3. The patient has sputum eosinophils 2% or higher while on high-dose inhaled corticosteroids or daily oral corticosteroids AND
      2. The patient has a history of uncontrolled asthma while on asthma control therapy as demonstrated by ONE of the following:
         1. Frequent severe asthma exacerbations requiring two or more courses of systemic corticosteroids (steroid burst) within the past 12 months OR
         2. Serious asthma exacerbations requiring hospitalization, mechanical ventilation, or visit to the emergency room or urgent care within the past 12 months OR
         3. Controlled asthma that worsens when the doses of inhaled and/or systemic corticosteroids are tapered OR
         4. The patient has baseline (prior to therapy with the requested agent) Forced Expiratory Volume (FEV1) that is less than 80% of predicted OR
   2. The patient has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and ALL of the following:
      1. The requested agent is FDA labeled or compendia supported for EGPA AND
      2. ONE of the following:
         1. The patient has a baseline (prior to therapy for the requested indication) blood eosinophilia greater than or equal to 1000 cells/microliter OR 
         2. The patient has a baseline (prior to therapy for the requested indication) blood eosinophil level greater than or equal to 10% eosinophils on white blood cell differential count AND
      3. The patient has a history or presence of asthma AND
      4. The patient does NOT have severe disease with organ- or life-threatening manifestations (e.g., alveolar hemorrhage, glomerulonephritis, central nervous system vasculitis, mononeuritis multiplex, cardiac involvement, mesenteric ischemia, limb/digit ischemia) AND
      5. ONE of the following:
         1. BOTH of the following:
            1. The patient is currently treated within the past 90 days with oral corticosteroid (OCS) therapy for at least 4 weeks AND
            2. The patient will be using oral corticosteroid (OCS) therapy in combination with the requested agent OR
         2. The patient has an intolerance or hypersensitivity to therapy with an oral corticosteroid (OCS) OR
         3. The patient has an FDA labeled contraindication to ALL oral corticosteroids AND
      6. The patient will be using the requested agent for ONE of the following:
         1. Treatment of relapsing/refractory disease OR
         2. Treatment for maintenance of disease remission OR
   3. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication OR
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
3. If the patient has a diagnosis of severe eosinophilic asthma, then ALL of the following:
   1. ONE of the following:
      1. The patient is NOT currently treated with the requested agent AND is currently treated with a maximally tolerated inhaled corticosteroid for at least 3 months AND has been adherent for 90 days within the past 120 days OR
      2. The patient is currently treated with the requested agent AND ONE of the following:
         1. The patient is currently treated with an inhaled corticosteroid for at least 3 months that is adequately dosed to control symptoms AND has been adherent for 90 days within the past 120 days OR
         2. The patient is currently treated with a maximally tolerated inhaled corticosteroid for at least 3 months AND has been adherent for 90 days within the past 120 days OR
      3. The patient has an intolerance or hypersensitivity to therapy with an inhaled corticosteroid OR
      4. The patient has an FDA labeled contraindication to ALL inhaled corticosteroids AND
   2. ONE of the following:
      1. The patient is currently treated for at least 3 months AND has been adherent for 90 days within the past 120 days with ONE of the following:
         1. A long-acting beta-2 agonist (LABA) OR
         2. A long-acting muscarinic antagonist (LAMA) OR
         3. A leukotriene receptor antagonist (LTRA) OR
         4. Theophylline OR
      2. The patient has an intolerance or hypersensitivity to therapy with a long-acting beta-2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), a leukotriene receptor antagonist (LTRA), or theophylline OR
      3. The patient has an FDA labeled contraindication to ALL long-acting beta-2 agonists (LABA) AND long-acting muscarinic antagonists (LAMA) AND
   3. The patient will continue asthma control therapy (e.g., ICS, ICS/LABA, LTRA, LAMA, theophylline) in combination with the requested agent AND
4. If the requested agent is Fasenra 30mg/mL prefilled syringe, then BOTH of the following:

3. ONE of the following (reference table above):
   1. The patient has tried a self-administered trial product for the requested agent OR
   2. There is support for the use of a provider-administered product over self-administered products AND
4. ONE of the following (reference table above):
   1. The requested agent does NOT require a preferred provider-administered trial product OR
   2. The patient has tried a preferred provider-administered trial product for the requested agent OR
   3. There is support for the use of the requested agent over ALL preferred provider-administered trial products AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, immunologist, otolaryngologist, pulmonologist, rheumatologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
6. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent AND
8. The requested quantity (dose) is within FDA labeled dosing (or supported in compendia) for the requested indication

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

4. Renewal Criteria

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Medical Drug Review process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. ONE of the following:
   1. The patient has a diagnosis of severe eosinophilic asthma AND BOTH of the following:
      1. The patient has had improvements or stabilization with the requested agent from baseline (prior to therapy with the requested agent) as indicated by ONE of the following:
         1. Increase in percent predicted Forced Expiratory Volume (FEV1) OR
         2. Decrease in the dose of inhaled corticosteroids required to control the patient’s asthma OR
         3. Decrease in need for treatment with systemic corticosteroids due to exacerbations of asthma OR
         4. Decrease in number of hospitalizations, need for mechanical ventilation, or visits to urgent care or emergency room due to exacerbations of asthma AND
      2. The patient is currently treated within the past 90 days and is compliant with asthma control therapy (e.g., inhaled corticosteroids [ICS], ICS/long-acting beta-2 agonist [ICS/LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist [LAMA], theophylline) OR
   2. The patient has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) AND the patient has had improvements or stabilization with the requested agent from baseline (prior to therapy with the requested agent) as indicated by ONE of the following:
      1. Remission achieved with the requested agent OR
      2. Decrease in oral corticosteroid maintenance dose required for control of symptoms related to EGPA OR
      3. Decrease in hospitalization due to symptoms of EGPA OR
      4. Dose of maintenance corticosteroid therapy and/or immunosuppressant therapy was not increased OR
   3. The patient has a diagnosis other than severe eosinophilic asthma, EGPA AND has had clinical benefit with the requested agent AND
3. If the requested agent is Fasenra 30mg/mL prefilled syringe, then BOTH of the following:

3. ONE of the following (reference table above):
   1. The patient has tried a self-administered trial product for the requested agent OR
   2. There is support for the use of a provider-administered product over self-administered products AND
4. ONE of the following (reference table above):
   1. The requested agent does NOT require a preferred provider-administered trial product OR
   2. The patient has tried a preferred provider-administered trial product for the requested agent OR
   3. There is support for the use of the requested agent over ALL preferred provider-administered trial products AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, immunologist, otolaryngologist, pulmonologist, rheumatologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
6. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent AND
8. The requested quantity (dose) is within FDA labeled dosing (or supported in compendia) for the requested indication

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

5. Dosage/Administration

6. Billing Code/Availability Information

HCPCS Code:

• J0517 - Injection, benralizumab, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Fasenra 10 mg/0.5 mL single-dose prefilled syringe: 00310-1745-xx
• Fasenra 30 mg/mL single-dose prefilled syringe: 00310-1730-xx
• Fasenra 30 mg/mL single-dose autoinjector FASENRA PEN: 00310-1830-xx

7. References

1. Fasenra [package insert]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; September 2024. Accessed September 2024.
2. National Asthma Education and Prevention Program (NAEPP). Guidelines for the diagnosis and management of asthma. Expert Panel Report 3. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); August 2007.
3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019 Update. Available from: http://www.ginasthma.org. Accessed September 2020.
4. Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014; 7: 53–65.
5. Goldman M, Hirsch I, Zangrilli JG, et al. The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies. Curr Med Res Opin. 2017 Sep;33(9):1605-1613. Doi: 10.1080/03007995.2017.1347091. Epub 2017 Jul 19.
6. The Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2017. Available from: www.ginasthma.org.
7. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS Guidelines on Definition, Evaluation, and Treatment of Severe Asthma. Eur Respir J 2014; 43: 343-373.
8. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European

Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020; 55: 1900588 [https://doi.org/10.1183/13993003.00588-2019].

9. National Asthma Education and Prevention Program (NAEPP). 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); December 2020.
10. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2021 Update. Available from: http://www.ginasthma.org. Accessed June 2021.
11. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2022 Update. Available from: http://www.ginasthma.org. Accessed September 2023.
12. Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. 2023 Update. Available from: http://www.ginasthma.org/2023-gina-main-report. Accessed September 2023.
13. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5. PMID: 27609408.
14. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2128-2141. Doi: 10.1016/S0140-6736(16)31322-8. Epub 2016 Sep 5. PMID: 27609406.
15. Nair P, Wenzel S, Rabe KF, et al; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22. PMID: 28530840.
16. Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. 2024 Update. Available from: http://www.ginasthma.org. Accessed August 2024.
17. Wechsler ME, Nair P, Terrier B, et al; MANDARA Study Group. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024 Mar 7;390(10):911-921. doi: 10.1056/NEJMoa2311155. Epub 2024 Feb 23. PMID: 38393328.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A