Restricted Product(s):

• benralizumab (Fasenra^®) subcutaneous injection for administration by a healthcare professional
• mepolizumab (Nucala^®) subcutaneous injection for administration by a healthcare professional
• reslizumab (Cinqair^®) intravenous infusion for administration by a healthcare professional

FDA Approved Use:

• Benralizumab (Fasenra^®)
  • Add-on maintenance treatment for severe asthma in adults and children 6 years or older with an eosinophilic phenotype
  • Treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA)
  • Limitations of use: Not for relief of acute bronchospasm or status asthmaticus
• Mepolizumab (Nucala^®)
  • Add-on maintenance treatment for severe asthma in adults and children 6 years or older with an eosinophilic phenotype
  • Treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA)
  • Treatment of adults and children 12 years or older with hypereosinophilic syndrome (HES) for at least 6 months without an identifiable non-hematologic secondary cause
  • Add-on maintenance treatment of adult patients 18 years or older with chronic rhinosinusitis with nasal polyps (CRSwNP)
  • Limitations of use: Not for relief of acute bronchospasm or status asthmaticus
• Reslizumab (Cinqair^®)
  • Add-on maintenance treatment for severe asthma in patients 18 years or older with an eosinophilic phenotype
  • Limitations of use: Not for treatment of other eosinophilic conditions or for relief of acute bronchospasm or status asthmaticus

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

*For patients that are new to the plan and currently using the medication, the criteria pertain to when the patient started the medication.

1. The patient has a diagnosis of severe eosinophilic asthma; AND
   1. The patient is 18 years of age or older; OR
   2. If the request is for benralizumab (Fasenra) or mepolizumab (Nucala), the patient is 6 years of age or older; AND
   3. The patient has one of the following:
      1. If the request is for benralizumab (Fasenra) or mepolizumab (Nucala):
         1. Eosinophil counts greater than or equal to 150 cells/microliter at initiation of therapy (i.e., within the past 6 weeks);
            OR
         2. Eosinophil counts greater than or equal to 300 cells/microliter in the past 12 months; AND
      2. If the request is for reslizumab (Cinqair):
         1. Eosinophil counts greater than or equal to 400 cells/microliter at initiation of therapy (i.e., within the past 6 weeks);
            OR
         2. Eosinophil counts greater than or equal to 400 cells/microliter in the past 12 months; AND
   4. The patient does NOT have neoplastic disease or known/suspected parasitic infection; AND
   5. The patient has had two or more exacerbations in the past year despite adherence to therapy with:
      1. 12 months of high-dose inhaled corticosteroid (ICS) given in combination with a minimum of 3 months of controller medication (either a long-acting beta2-agonist [LABA], or leukotriene receptor antagonist [LTRA], or theophylline), unless the patient is intolerant of, or has a medical contraindication to these medications; OR
      2. 6 months of ICS with daily oral glucocorticoids given in combination with a minimum of 3 months of controller medication (either a LABA, or LTRA, or theophylline), unless the patient is intolerant of, or has a medical contraindication to these medications; OR
2. The patient has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss Syndrome); AND
   1. The request is for benralizumab (Fasenra) or mepolizumab (Nucala); AND
   2. The patient is 18 years of age or older; AND
   3. The patient is stable on oral corticosteroids; AND
   4. The patient has tried and failed or has a clinical intolerance/contraindication to an oral immunosuppressant (e.g., cyclophosphamide, azathioprine, methotrexate, leflunomide, mycophenolate mofetil); OR
3. The patient has a diagnosis of hypereosinophilic syndrome (HES); AND
   1. The request is for mepolizumab (Nucala); AND
   2. The patient is 12 years of age or older; AND
   3. The patient has been diagnosed for six months or greater; AND
   4. The patient does NOT have non-hematologic secondary HES (e.g., drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy) or FIP1L1-PDGFRα kinase-positive HES; AND
   5. The patient has been on stable dosing of and will continue HES therapy (e.g., oral corticosteroids, immunosuppressive agents and/or cytotoxic therapy); AND
   6. The patient has had at least two HES flares in the past 12 months (one of which was NOT related to a decrease in HES therapy within 4 weeks prior to flare) defined as:
      1. HES-related worsening of clinical symptoms; OR
      2. Blood eosinophil count requiring escalation in therapy; AND
   7. The patient has a blood eosinophil count greater than or equal to 1,000 cells/microliter; OR
4. The patient has a diagnosis of chronic rhinosinusitis with nasal polyposis (CRSwNP); AND
   1. The request is for mepolizumab (Nucala); AND
   2. The patient is 18 years of age or older; AND
   3. The patient has tried and failed or has a clinical intolerance/contraindication to Xhance (fluticasone propionate nasal spray) [medical record documentation required]; OR
   4. The patient has tried and failed or has a clinical intolerance/contraindication to oral systemic corticosteroids within the previous 6months [medical record documentation required]; AND
   5. ONE of the following:
      1. The patient has had prior surgery for nasal polyps [medical record documentation required]; OR
      2. The patient is not a candidate for sinus surgery [medical record documentation required]; AND
   6. The patient will not be using Nucala (mepolizumab) in combination with Xhance (fluticasone propionate nasal spray); AND
   7. ONE of the following:
      1. The patient is currently being treated with an over the counter intranasal steroid; OR
      2. The patient has a clinical intolerance/contraindication to ALL intranasal steroids [medical record documentation required];
         AND
5. The patient will NOT receive the requested agent in combination with another biologic immunomodulator agent used for the same indication [e.g., benralizumab (Fasenra), dupilumab (Dupixent), mepolizumab (Nucala), omalizumab (Xolair), reslizumab (Cinqair)]; AND
6. For reslizumab (Cinqair) requests, ONE of the following:
   1. The patient has tried and had an inadequate response to benralizumab (Fasenra) AND mepolizumab (Nucala) [medical record documentation required]; OR
   2. The patient has a clinical intolerance, FDA labeled contraindication, or hypersensitivity to benralizumab (Fasenra) AND mepolizumab (Nucala) [medical record documentation required]; AND
7. For mepolizumab (Nucala) or benralizumab (Fasenra) requests, the patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]:
   1. Inability to self-administer the medication; AND
   2. Lack of caregiver or support system for assistance with administration of self-administered products; AND
8. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
9. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year) 365 days (1 year)

Continuation Criteria for Approval:

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy; AND
3. For patients with a diagnosis of severe eosinophilic asthma, they have demonstrated one or more of the following while using the medication [medical record documentation required]:
   1. Decreased utilization of rescue medications;
   2. Decreased frequency of exacerbations (defined as worsening of asthma that requires an increase in ICS dose or treatment with systemic corticosteroids);
   3. Increase in predicted FEV1 from pretreatment baseline;
   4. Reduction in reported asthma-related symptoms, such as, asthmatic symptoms upon awakening, coughing, fatigue, shortness of breath, sleep disturbance, or wheezing; OR
4. For patients using benralizumab (Fasenra) or mepolizumab (Nucala) for eosinophilic granulomatosis with polyangiitis, the patient is stable on oral corticosteroid therapy; OR
5. For patients using mepolizumab (Nucala) for hypereosinophilic syndrome (HES), they have demonstrated one or more of the following while using the medication [medical record documentation required]:
   1. Reduction in number of flares from baseline; OR
   2. Improvement in clinical symptoms (e.g., fatigue severity, cough, breathlessness); OR
6. For patients using mepolizumab (Nucala) for chronic rhinosinusitis with nasal polyposis (CRSwNP):
   1. The patient has been on and adherent to an over the counter intranasal steroid since starting mepolizumab (Nucala) therapy [medical record documentation required]; OR
   2. The patient has a clinical intolerance/contraindication to ALL intranasal steroids [medical record documentation required]; AND
7. The patient will NOT receive the requested agent in combination with another biologic immunomodulator agent used for the same indication [e.g., benralizumab (Fasenra), dupilumab (Dupixent), mepolizumab (Nucala), omalizumab (Xolair), reslizumab (Cinqair)]; AND
8. For reslizumab (Cinqair) requests, ONE of the following:
   1. The patient has tried and had an inadequate response to benralizumab (Fasenra) AND mepolizumab (Nucala) [medical record documentation required]; OR
   2. The patient has a clinical intolerance, FDA labeled contraindication, or hypersensitivity to benralizumab (Fasenra) AND mepolizumab (Nucala) [medical record documentation required]; AND
9. For mepolizumab (Nucala) or benralizumab (Fasenra) requests, the patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]:
   1. Inability to self-administer the medication; AND
   2. Lack of caregiver or support system for assistance with administration of self-administered products; AND
10. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
11. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)