Last Review Date: 01/06/2025

Date of Origin: 12/04/2015

Dates Reviewed: 12/2015, 07/2016, 03/2017, 06/2017, 09/2017, 12/2017, 01/2018, 03/2018, 06/2018, 10/2018, 10/2019, 01/2020, 10/2020, 03/2021, 08/2021, 02/2022, 10/2022, 10/2023, 10/2024, 01/2025

1. Length of Authorization

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

2. Dosing Limits

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

Severe Eosinophilic Asthma

• 100 billable units every 28 days

EGPA

• 300 billable units every 28 days

Hypereosinophilic Syndrome

• 300 billable units every 28 days

CRSwNP

• 100 billable units every 28 days

3. 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
   2. 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 or refractory disease OR
               2. Treatment for maintenance of disease remission OR
         3. The patient has a diagnosis of hypereosinophilic syndrome (HES) and ALL of the following:
            1. The requested agent is FDA labeled or compendia supported for HES AND
            2. The patient has had a diagnosis of HES for at least 6 months AND
            3. The patient’s diagnosis of HES was confirmed by BOTH of the following:
               1. ONE of the following:
                  1. The patient has a peripheral blood eosinophil count greater than 1000 cells/microliter OR
                  2. The patient has a percentage of eosinophils in bone marrow section exceeding 20% of all nucleated cells OR
                  3. The patient has marked deposition of eosinophil granule proteins found OR
                  4. The patient has tissue infiltration by eosinophils that is extensive in the opinion of a pathologist AND
               2. There has been evaluation of hypereosinophilia-related organ involvement (e.g., fibrosis of lung, heart, digestive tract, skin; thrombosis with or without thromboembolism; cutaneous erythema, edema/angioedema, ulceration, pruritis, or eczema; peripheral or central neuropathy with chronic or recurrent neurologic deficit; other organ system involvement such as liver, pancreas, kidney) AND
            4. The patient does NOT have an identifiable non-hematologic secondary (reactive) cause of HES (e.g., infection [e.g., HIV infection or parasitic helminth infection], allergy/atopy, medications [e.g., drug hypersensitivity], collagen vascular disease, metabolic [e.g., adrenal insufficiency], solid tumor/lymphoma [e.g., non-hematologic malignancy]) AND
            5. The patient does NOT have FIP1L1-PDGFRA-positive disease AND
            6. The patient has a history of at least 2 HES flares within the past 12 months (i.e., worsening of clinical symptoms and/or blood eosinophil counts requiring an escalation in therapy) AND
            7. ONE of the following:
               1. The patient has tried and had an inadequate response to ONE of the following:
                  1. Oral corticosteroid (OCS) therapy OR
                  2. Hydroxyurea OR
                  3. Interferon-a OR
                  4. Another immunosuppressive agent (e.g., cyclosporine, methotrexate) OR
               2. The patient has an intolerance or hypersensitivity to therapy with an oral corticosteroid, hydroxyurea, interferon-a, or an immunosuppressive agent (e.g., cyclosporine, methotrexate) used in the treatment of HES OR
               3. The patient has an FDA labeled contraindication to hydroxyurea, interferon-a, and ALL oral corticosteroids and immunosuppressive agents (e.g., cyclosporine, methotrexate) used in the treatment of HES OR
         4. The patient has a diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) AND ALL of the following:
            1. The requested agent is FDA labeled or compendia supported for CRSwNP AND
            2. The patient has at least TWO of the following symptoms consistent with chronic rhinosinusitis (CRS): 
               1. Nasal discharge (rhinorrhea or post-nasal drainage) 
               2. Nasal obstruction or congestion
               3. Loss or decreased sense of smell (hyposmia)
               4. Facial pressure or pain AND
            3. The patient has had symptoms consistent with chronic rhinosinusitis (CRS) for at least 12 consecutive weeks AND
            4. The patient’s diagnosis was confirmed by ONE of the following:
               1. Anterior rhinoscopy or endoscopy OR
               2. Computed tomography (CT) of the sinuses AND
            5. ONE of the following:
               1. The patient has tried and had an inadequate response to ONE intranasal corticosteroid therapy (e.g., fluticasone nasal spray, mometasone nasal spray, Sinuva) after at least a 4-week duration of therapy OR
               2. The patient has an intolerance or hypersensitivity to ONE intranasal corticosteroid therapy (e.g., fluticasone nasal spray, mometasone nasal spray, Sinuva) OR
               3. The patient has an FDA labeled contraindication to ALL intranasal corticosteroids OR
         5. 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
2. 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
3. If the patient has a diagnosis of hypereosinophilic syndrome (HES), then the patient will continue existing HES therapy (e.g., OCS, hydroxyurea, interferon-a, immunosuppressant) in combination with the requested agent AND
4. If the patient has a diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP), then BOTH of the following:
   1. The patient is currently treated with standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids [e.g., fluticasone nasal spray, mometasone nasal spray, Sinuva]) AND
   2. The patient will continue standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids [e.g., fluticasone nasal spray, mometasone nasal spray, Sinuva]) in combination with the requested agent AND
5. If the requested agent is Nucala vial, then BOTH of the following:

5. 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
6. 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
7. 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
8. 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
9. The patient does NOT have any FDA labeled contraindications to the requested agent AND
10. 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 of hypereosinophilic syndrome (HES) 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. Decrease in incidence of HES flares OR
         2. Escalation of therapy (due to HES-related worsening of clinical symptoms or increased blood eosinophil counts) has NOT been required AND
      2. The patient will continue existing HES therapy (e.g., OCS, hydroxyurea, interferon-a, immunosuppressant) in combination with the requested agent OR
   4. The patient has a diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) AND BOTH of the following:
      1. The patient has had clinical benefit with the requested agent AND
      2. The patient will continue standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids [e.g., fluticasone nasal spray, mometasone nasal spray, Sinuva]) in combination with the requested agent OR
   5. The patient has a diagnosis other than severe eosinophilic asthma, EGPA, HES, or CRSwNP AND has had clinical benefit with the requested agent AND
3. If the requested agent is Nucala vial, 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:

• J2182 - Injection, mepolizumab, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Nucala 100 mg/mL lyophilized powder single-dose vial: 00173-0881-xx
• Nucala 100 mg/mL single-dose prefilled autoinjector or syringe (cartons of 1): 00173-0892-xx
• Nucala 40 mg/0.4 mL single-dose prefilled syringe (cartons of 1): 00173-0904-xx

7. References

1. Nucala [package insert]. Philadelphia, PA; GlaxoSmithKline LLC; March 2023. Accessed August 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 2023.
4. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079.
5. Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on antineutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007; 66: 605-17.
6. Masi AT, Hunder GG, Lie JT; Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum.  1990; 33(8):1094-100 (ISSN: 0004-3591).
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. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94. doi: 10.1136/annrheumdis-2016-209133.
9. Groh M, Panoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. European Journal of Internal Medicine 26 (2015) 545–553.
10. 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]
11. Roufosse F, Kahn JE, Rothenberg ME, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a Phase III, randomized, placebo-controlled trial.  Journal of Allergy and Clinical Immunology (2020), doi: https://doi.org/10.1016/j.jaci.2020.08.037.
12. 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.
13. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2021 Update.  Available from: http://www.ginasthma.org. Accessed September 2023.
14. Han JK, Bachert C, Fokkens W, et al; SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Apr 16:S2213-2600(21)00097-7. doi: 10.1016/S2213-2600(21)00097-7.
15. Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy. 2019;74:2312–2319. DOI: 10.1111/all.13875.

16. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.
17. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2022 Update. Available from: http://www.ginasthma.org. Accessed September 2023.
18. Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology 2023; 61:194.
19. 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.
20. Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):309-314. doi: 10.1136/annrheumdis-2021-221794.
21. Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. 2024 Update. Available from: http://www.ginasthma.org. Accessed August 2024.
22. Chipps BE, Jarjour N, Calhoun WJ, et al. A Comprehensive Analysis of the Stability of Blood Eosinophil Levels. Ann Am Thorac Soc. 2021 Dec; 18(12):1978-1987. doi: 10.1513/AnnalsATS.202010-1249OC.  
23. Chung, SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken) 2021; 73:1088.
24. Rank MA, Chu DK, Bognanni A, et al. The Joint Task Forcer on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis. J Allergy Clin Immunol. 2023 Feb; 151(2):386-398. doi: https://doi.org/10.1016/j.jaci.2022.10.026.  

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