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Mepolizumab is a recombinant, humanized monoclonal antibody specific to interleukin-5 (IL-5), the major cytokine responsible for growth, differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 and inhibits its interaction with the alpha subunit of the IL-5 receptor (IL-5R-alpha) on the surface of eosinophils, thereby reducing the production and survival of these cells. Mepolizumab is administered by subcutaneous injection by a healthcare professional.

The U.S. Food and Drug Administration (FDA) has approved mepolizumab (Nucala®) for the following indications:

• Add-on maintenance treatment of patients with severe asthma aged 6 years and older, and with an eosinophilic phenotype.
• Treatment of adult patients with eosinophilic granulomatosis with polyangiitis.
• Treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for ≥ 6 months without an identifiable non-hematologic secondary cause.

According to the prescribing information, mepolizumab is not indicated for relief of acute bronchospasm or status asthmaticus. Hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with mepolizumab

NOTE: When mepolizumab (Nucala®) will be self-administered, please refer to applicable pharmacy benefit plan.

I.   Initial Review for Mepolizumab (Nucala®)

Mepolizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Diagnosis of ONE of the following:
  • Severe eosinophilic asthma AND ALL of the following:
    1. Age 6 years or older; AND
    2. Blood eosinophil level is ONE of the following:
       • ≥150 cells/µL prior to initiating therapy; or
       • ≥300 cells/µL within the previous 12 months; AND
    3. Used as add-on therapy for patients currently receiving regular maintenance treatment with BOTH of the following:
       • Maximally tolerated inhaled corticosteroid OR documented intolerance, FDA labeled contraindication, or hypersensitivity to inhaled corticosteroids; and
       • An additional asthma controller medication (long-acting beta-2 agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist, or theophylline) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to controller medications; AND
    4. ONE of the following:
       • History of 2 or more asthma exacerbations requiring systemic corticosteroid treatment within the previous 12 months; or
       • Serious asthma exacerbation requiring hospitalization, mechanical ventilation, or visit to the emergency room or urgent care within the previous 12 months; or
       • Require daily oral corticosteroid therapy in addition to regular maintenance treatment, as defined above; or
       • Controlled asthma that worsens when the doses of inhaled or systemic corticosteroids are tapered; or
       • Pretreatment forced expiratory volume in 1 second (FEV1) <80% predicted;
         
       • AND
    5. Prescribed by or in consultation with a pulmonologist, allergist, or immunologist; OR
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) AND ALL of the following:
    1. Age 18 years or older; AND
    2. History or presence of asthma; AND
    3. Blood eosinophil level is ONE of the following:
       • ≥10% of leukocytes; or
       • Absolute eosinophil count >1,000 cells/µL; AND
    4. TWO OR MORE of the following:
       • Histopathological evidence of eosinophilic vasculitis, perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation;
       • Neuropathy;
       • Pulmonary infiltrates;
       • Sinonasal abnormalities;
       • Cardiomyopathy;
       • Glomerulonephritis;
       • Alveolar hemorrhage;
       • Palpable purpura;
       • Antineutrophil cytoplasmic antibody (ANCA)-positive; AND
    5. Used as add-on therapy for patients currently receiving maximally tolerated oral corticosteroid therapy OR documented intolerance, FDA labeled contraindication, or hypersensitivity to oral corticosteroid therapy; AND
    6. Previously tried and failed an immunosuppressant (e.g., azathioprine, methotrexate) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to immunosuppressants; AND
    7. Prescribed by or in consultation with a pulmonologist, rheumatologist, allergist, or immunologist; 
  • OR
  • Hypereosinophilic syndrome (HES) AND ALL of the following: 
    1. Age 12 years or older; AND 
    2. History of hypereosinophilic syndrome (HES) for ≥ 6 months; AND 
    3. Absence of non-hematologic secondary HES (e.g. drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy) or FIP1L1-PDGFRα kinase-positive HES; AND 
    4. Blood eosinophil level is ≥ 1,000 cells/µL; AND 
    5. Used as add-on therapy for patients currently receiving regular maintenance treatment for HES (e.g. oral corticosteroids, immunosuppressive, or cytotoxic therapy) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to HES therapy; AND 
    6. Prescribed by or in consultation with a hematologist, allergist, or immunologist; 
       
• AND
• No current infections requiring systemic treatment; AND
  
• Not used in combination with reslizumab (Cinqair®), benralizumab (Fasenra®), omalizumab (Xolair®), or dupilumab (Dupixent®); AND
• No FDA labeled contraindications to mepolizumab (see table 1 below); AND
• The dose is within the FDA labeled dose for the indication (see table 2 below);  AND
• For commercial health plan members only, mepolizumab is administered in accordance with site of service criteria (see policy XI-06); AND
  
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

II.  Renewal Review for Mepolizumab (Nucala®)

Mepolizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for mepolizumab through the initial review process; AND
• Demonstrated positive clinical response to mepolizumab therapy. Examples include:
  • For patients with severe eosinophilic asthma, decreased use of rescue medications, decreased frequency of exacerbations, increase in percent predicted FEV₁, reduction in asthma-related symptoms;
  • For patients with eosinophilic granulomatosis with polyangiitis (EGPA), decreased frequency and/or severity of relapses, reduction or discontinuation of corticosteroid therapy, disease remission, reduction in EGPA-related symptoms, stabilization of disease progression; AND
  • For patients with hypereosinophilic syndrome (HES), reduction of maintenance therapy for HES (e.g. oral corticosteroids, immunosuppressive, or cytotoxic therapy), reduction in HES-related symptoms, stabilization of disease progression;
• AND
• Used as add-on therapy for patients currently receiving standard maintenance treatment with the following:
  • For patients with severe eosinophilic asthma, currently receiving regular maintenance treatment with a maximally tolerated inhaled corticosteroid AND an additional asthma controller medication (long-acting beta-2 agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist, or theophylline) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to inhaled corticosteroids and controller medications;
  • For patients with EGPA, currently receiving maximally tolerated oral corticosteroid therapy OR documented intolerance, FDA labeled contraindication, or hypersensitivity to oral corticosteroid therapy; 
  • For patients with HES, currently receiving regular maintenance treatment for HES (e.g. oral corticosteroids, immunosuppressive, or cytotoxic therapy) OR documented intolerance, FDA labeled contraindication, or hypersensitivity to HES therapy;
    
• AND
• No current infections requiring systemic treatment; AND
  
• Prescribed by or in consultation with a pulmonologist, rheumatologist (EGPA only), hematologist (HES only), allergist, or immunologist; AND
• Not used in combination with reslizumab (Cinqair®), benralizumab (Fasenra®), omalizumab (Xolair®), or dupilumab (Dupixent®); AND
  
• No FDA labeled contraindications to mepolizumab (see table 1 below); AND
• The dose is within the FDA labeled dose for the indication (see table 2 below); AND
• For commercial health plan members only, mepolizumab is administered in accordance with site of service criteria (see policy XI-06).
  

III. Experimental/Investigative Uses

All other uses of mepolizumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1. FDA Labeled Contraindications

Table 2. Dosing

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization, when prior authorization is required. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
3. Laboratory documentation of blood eosinophil level.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for mepolizumab administration is specified, including CMS place of service code (see policy XI-06). If mepolizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.
6. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).

Renewal Review

1. Documentation of prior approval for mepolizumab through the initial review process.
2. Documentation supporting positive clinical response.
3. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for mepolizumab administration is specified, including CMS place of service code (see policy XI-06). If mepolizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.