Monoclonal Antibodies for the Treatment of Eosinophilic Conditions (ARCHIVED)

Policy ID: I-9146-005

Section: Injections

Effective Date: January 01, 2022

Revised Date: October 20, 2024

Revision Effective Date: December 08, 2024

Last Reviewed: November 19, 2024

Applies To: Commercial Only

**This policy has been Archived effective December 08, 2024. Click the Archive tab above for more information.**

Policy ID: I-9146-005

Section: Injections

Effective Date: January 01, 2022

Revised Date: October 20, 2024

Revision Effective Date: December 08, 2024

Last Reviewed: November 19, 2024

Archived Date: December 08, 2024

Applies To: Commercial Only

Description

Benralizumab (Fasenra ^TM ) is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for add-on maintenance treatment of individuals with severe asthma aged 12 years and older, and with an eosinophilic phenotype.

Benralizumab (Fasenra) prefilled syringe may be covered on the medical benefit. Benralizumab (Fasenra) autoinjector may be covered on the pharmacy benefit.

Mepolizumab (Nucala ^® ) is a humanized monoclonal antibody against interleukin-5 (IL-5). IL-5 is the predominant cytokine responsible for the growth and differentiation, recruitment, activation and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inhibition of IL-5 signaling reduces the production and survival of eosinophils.

Mepolizumab (Nucala) vial may be covered on the medical benefit. Mepolizumab (Nucala) autoinjector and prefilled syringe may be covered on the pharmacy benefit.

Reslizumab (Cinqair ^® ) is an interleukin-5 antagonist monoclonal antibody (IgG4 kappa) indicated for add-on maintenance treatment of individuals with severe asthma aged 18 years and older, and with an eosinophilic phenotype.

Policy Application

All claims submitted for this policy will be processed according to the policy effective date and associated revision effective dates in effect on the date of service.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Benralizumab (Fasenra) prefilled syringe, mepolizumab (Nucala) vial or reslizumab (Cinqair) may be considered medically necessary when ALL of the following are met:

If the individual has a Food and Drug Administration (FDA) approved indication, then ONE of the following:
- The individual's age is within FDA labeling for the requested indication for the requested agent; or
- The prescriber has provided information in support of using the requested agent for the individual's age for the requested indication; and
ONE of the following:
- The individual has a diagnosis of severe eosinophilic asthma and ALL of the following:
  1. The individual's diagnosis has been confirmed by ONE of the following:
    1. The individual has a baseline (prior to therapy with the requested agent) blood eosinophilic count of 150 cells/microliter or higher while on high-dose inhaled corticosteroids or daily oral corticosteroids; or
    2. The individual 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 individual has sputum eosinophils 2% or higher while on high-dose inhaled corticosteroids or daily oral corticosteroids; and
  2. The individual 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 individual has baseline (prior to therapy with the requested agent) Forced Expiratory Volume (FEV1) that is less than 80% of predicted; and
  3. ONE of the following:
    1. The individual is NOT currently being treated with the requested agent AND is currently treated with a maximally tolerated inhaled corticosteroid for at least three (3) months; or
    2. The individual is currently being treated with the requested agent AND ONE of the following:
      1. Is currently treated with an inhaled corticosteroid for at least three (3) months that is adequately dosed to control symptoms; or
      2. Is currently treated with a maximally tolerated inhaled corticosteroid for at least three (3) months; or
    3. The individual has an intolerance or hypersensitivity to inhaled corticosteroid therapy; or
    4. The individual has an FDA labeled contraindication to ALL inhaled corticosteroids; and
  4. ONE of the following:
    1. The individual is currently being treated for at least three (3) months with ONE of the following:
      1. A long-acting beta-2 agonist (LABA); or
      2. A leukotriene receptor antagonist (LTRA); or
      3. Long-acting muscarinic antagonist (LAMA); or
      4. Theophylline; or
    2. The individual has an intolerance or hypersensitivity to therapy with long-acting beta-2 agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA), or theophylline; or
    3. The individual has an FDA labeled contraindication to ALL long-acting beta-2 agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA), AND theophylline; and
  5. The individual will continue asthma control therapy (e.g., ICS, ICS/LABA, LTRA, LAMA, theophylline) in combination with the requested agent; and
  6. If the requested agent is reslizumab (Cinqair), the individual has a baseline (prior to therapy with the requested agent) blood eosinophil count of 400 cells/microliter or higher; or
- The individual has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. The individual has had a diagnosis of EGPA for at least 6 months with a history of relapsing or refractory disease; and
  3. The individual's diagnosis of EGPA was confirmed by ONE of the following:
    1. The individual meets four (4) of the following:
      1. Asthma (history of wheezing or diffuse high-pitched rales on expiration)
      2. Eosinophilia (greater than 10% eosinophils on white blood cell differential count)
      3. Mononeuropathy (including multiplex), multiple mononeuropathies, or polyneuropathy attributed to a systemic vasculitis
      4. Migratory or transient pulmonary infiltrates detected radiographically
      5. Paranasal sinus abnormality
      6. Biopsy containing a blood vessel showing the accumulation of eosinophils in extravascular areas; or
    2. The individual meets ALL of the following:
      1. Medical history of asthma; and
      2. Peak peripheral blood eosinophilia greater than 1500 cells/microL; and
      3. Systemic vasculitis involving two (2) or more extra-pulmonary organs; and
  4. ONE of the following:
    1. The individual is currently on maximally tolerated oral corticosteroid therapy; or
    2. The individual has an intolerance or hypersensitivity to oral corticosteroid therapy; or
    3. The individual has an FDA labeled contraindication to ALL oral corticosteroids; and
  5. ONE of the following:
    1. The individual has tried and had an inadequate response to ONE oral immunosuppressant (i.e., azathioprine, methotrexate, mycophenolate mofetil); or
    2. The individual has an intolerance or hypersensitivity to oral immunosuppressant therapy; or
    3. The individual has an FDA labeled contraindication to ALL oral immunosuppressants; or
- The individual has a diagnosis of hypereosinophilic syndrome (HES) and ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. BOTH of the following:
    1. The individual has had a diagnosis of HES for at least six (6) months; and
    2. The individual has a history of at least two (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
  3. The individual's diagnosis of HES was confirmed by BOTH of the following:
    1. ONE of the following:
      1. The individual has a peripheral blood eosinophil count greater than 1500 cells/microliter; or
      2. The individual has a percentage of eosinophils in bone marrow section exceeding 20% of all nucleated cells; or
      3. The individual has marked deposition of eosinophil granule proteins found; or
      4. The individual has tissue infiltration by eosinophils that is extensive in the opinion of a pathologist; and
    2. ALL of the following:
      1. Secondary (reactive, non-hematologic) causes of eosinophilia have been excluded (e.g., infection, allergy/atopy, medications, collagen vascular disease, metabolic [e.g., adrenal insufficiency], solid tumor/lymphoma); and
      2. There is evidence of hypereosinophilia-related organ damage (e.g., fibrosis of lung, heart, digestive tract, skin, etc; 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
      3. The individual does NOT have FIP1L1-PDGFRA-positive disease; and
  4. ONE of the following:
    1. The individual is currently being treated with maximally tolerated oral corticosteroid (OCS); or
    2. The individual has an intolerance or hypersensitivity to oral corticosteroid (OCS) therapy; or
    3. The individual has an FDA labeled contraindication to ALL oral corticosteroids; and
  5. ONE of the following:
    1. The individual is currently being treated with ONE of the following:
      1. Hydroxyurea; or
      2. Interferon-α; or
      3. Another immunosuppressive agent (e.g., azathioprine, cyclosporine, methotrexate, tacrolimus); or
    2. The individual has an intolerance or hypersensitivity to therapy with hydroxyurea, interferon-α, or immunosuppressive agents (e.g., azathioprine, cyclosporine, methotrexate, tacrolimus); or
    3. The individual has an FDA labeled contraindication to hydroxyurea, interferon-α, and ALL immunosuppressive agents (e.g., azathioprine, cyclosporine, methotrexate, tacrolimus); and
  6. The individual will continue existing HES therapy (e.g., OCS, hydroxyurea, interferon-α, immunosuppressants) in combination with the requested agent; or
- The individual has a diagnosis of chronic rhinosinusitis with nasal polyposis (CRSwNP) AND ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. The individual has at least TWO of the following symptoms consistent with chronic rhinosinusitis (CRS):
    1. Nasal discharge (rhinorrhea or post-nasal drainage); or
    2. Nasal obstruction or congestion; or
    3. Loss or decreased sense of smell (hyposmia); or
    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. There is information indicating the individual'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. ONE of the following:
      1. The individual had an inadequate response to sinonasal surgery; or
      2. The individual is NOT a candidate for sinonasal surgery; or
    2. ONE of the following:
      1. The individual has tried and had an inadequate response to oral systemic corticosteroids; or
      2. The individual has an intolerance or hypersensitivity to therapy with oral systemic corticosteroids; or
      3. The individual has an FDA labeled contraindication to ALL oral systemic corticosteroids; and
  6. ONE of the following:
    1. The individual has tried and had an inadequate response to intranasal corticosteroids (e.g., fluticasone, Sinuva) used for at least a three (3)-month trial; or
    2. The individual has an intolerance or hypersensitivity to therapy with intranasal corticosteroids (e.g., fluticasone, Sinuva); or
    3. The individual has an FDA labeled contraindication to ALL intranasal corticosteroids; and
  7. BOTH of the following:
    1. The individual is currently treated with standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids); and
    2. The individual will continue standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids) in combination with the requested agent; or
- The individual has another FDA approved indication for the requested agent and route of administration; or
- The individual has another indication that is supported in compendia for the requested agent and route of administration; and
ONE of the following:
- The individual has tried a self-administered benralizumab (Fasenra) or mepolizumab (Nucala) product (i.e., Fasenra auto-injector pen; Nucala auto-injector or prefilled syringe); or
- The prescriber has provided information to support the use of the provider-administered product over the self-administered product; and
The prescriber is a specialist in the area of the individual's diagnosis (e.g., allergist, immunologist, otolaryngologist, pulmonologist) or the prescriber has consulted with a specialist in the area of the individual's diagnosis; and
ONE of the following:
- The individual will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors); or
- The prescriber has provided information in support of combination therapy (submitted copy required, e.g., clinical trials, phase III studies, guidelines required).

Reauthorization Criteria

Benralizumab (Fasenra) prefilled syringe, mepolizumab (Nucala) vial or reslizumab (Cinqair) may be considered medically necessary when ALL of the following are met:

The individual has been previously approved for the requested agent through the Blue Cross Blue Shield of North Dakota's precertification process; and
ONE of the following:
- The individual has a diagnosis of severe eosinophilic asthma AND BOTH of the following:
  1. The individual 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 (FEV ₁ ); or
    2. Decrease in the dose of inhaled corticosteroids required to control the individual'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 individual is currently treated and is compliant with asthma control therapy [i.e., inhaled corticosteroids (ICS), ICS/long-acting beta-2 agonist (ICS/LABA), leukotriene receptor antagonist (LTRA), long-acting muscarinic antagonist (LAMA), theophylline]; or
- The individual has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) AND ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. The individual 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; and
  3. ONE of the following:
    1. The individual is currently treated and is compliant with maintenance therapy with oral corticosteroids; or
    2. The individual has an intolerance or hypersensitivity to oral corticosteroid therapy; or
    3. The individual has an FDA labeled contraindication to ALL oral corticosteroids; or
- The individual has a diagnosis of hypereosinophilic syndrome (HES) AND ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. The individual 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
  3. ONE of the following:
    1. The individual is currently treated and is compliant with oral corticosteroid and/or other maintenance therapy (e.g., hydroxyurea, interferon-α, azathioprine, cyclosporine, methotrexate, tacrolimus); or
    2. The individual has an intolerance or hypersensitivity to therapy with oral corticosteroids or other maintenance agents (e.g., hydroxyurea, interferon-α, azathioprine, cyclosporine, methotrexate, tacrolimus); or
    3. The individual has an FDA labeled contraindication to ALL oral corticosteroids AND maintenance agents (e.g., hydroxyurea, interferon-α, azathioprine, cyclosporine, methotrexate, tacrolimus); or
- The individual has a diagnosis of chronic rhinosinusitis with nasal polyposis (CRSwNP) AND ALL of the following:
  1. The requested agent is mepolizumab (Nucala) vial; and
  2. The individual has had clinical benefit with the requested agent; and
  3. The individual will continue standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids) in combination with the requested agent; or
- The individual has another FDA approved indication for the requested agent and route of administration AND has received clinical benefit with the requested agent; or
- The individual has another indication that is supported in compendia for the requested agent and route of administration AND has received clinical benefit with the requested agent; and
ONE of the following:
- The individual has tried a self-administered benralizumab (Fasenra) or mepolizumab (Nucala) product (i.e., Fasenra auto-injector pen; Nucala auto-injector or prefilled syringe); or
- The prescriber has provided information to support the use of the provider-administered product over the self-administered product; and
The prescriber is a specialist in the area of the individual's diagnosis (e.g., allergist, immunologist, otolaryngologist, pulmonologist) or the prescriber has consulted with a specialist in the area of the individual's diagnosis; and
ONE of the following:
- The individual will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors); or
- The prescriber has provided information in support of combination therapy (submitted copy required, e.g., clinical trials, phase III studies, guidelines required).

Benralizumab (Fasenra) prefilled syringe, mepolizumab (Nucala) vial or reslizumab (Cinqair) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Codes

J0517

J2182

J2786

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the United States Food and Drug Administration (U.S. FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

NOTE: Compendia allowed are DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

Diagnosis Codes

Covered Diagnosis Codes for all Procedure Codes

J45.50

J45.51

J45.52

J82.83

J82.89

Additional Covered Diagnosis Codes for Procedure Code J2182

D72.110

D72.119

J33.0

J33.1

J33.8

J33.9

M30.1

Professional Statements and Societal Positions Guidelines

Agents NOT to be used Concomitantly (subject to change)

Abrilada (adalimumab-afzb)

Actemra (tocilizumab)

Adalimumab

Adbry (tralokinumab-ldrm)

Amjevita (adalimumab-atto)

Arcalyst (rilonacept)

Avsola (infliximab-axxq)

Benlysta (belimumab)

Cibinqo (abrocitinib)

Cimzia (certolizumab)

Cinqair (reslizumab)

Cosentyx (secukinumab)

Cyltezo (adalimumab-adbm)

Dupixent (dupilumab)

Enbrel (etanercept)

Entyvio (vedolizumab)

Fasenra (benralizumab)

Hadlima (adalimumab-bwwd)

Hulio (adalimumab-fkjp)

Humira (adalimumab)

Hyrimoz (adalimumab-adaz)

Idacio (adalimumab-aacf)

Ilaris (canakinumab)

Ilumya (tildrakizumab-asmn)

Inflectra (infliximab-dyyb)

Infliximab

Kevzara (sarilumab)

Kineret (anakinra)

Nucala (mepolizumab)

Olumiant (baricitinib)

Opzelura (ruxolitinib)

Orencia (abatacept)

Otezla (apremilast)

Remicade (infliximab)

Renflexis (infliximab-abda)

Riabni (rituximab-arrx)

Rinvoq (upadacitinib)

Rituxan (rituximab)

Rituxan Hycela (rituximab/hyaluronidase human)

Ruxience (rituximab-pvvr)

Siliq (brodalumab)

Simponi (golimumab)

Simponi ARIA (golimumab)

Skyrizi (risankizumab-rzaa)

Sotyktu (deucravacitinib)

Stelara (ustekinumab)

Taltz (ixekizumab)

Tezspire (tezepelumab-ekko)

Tremfya (guselkumab)

Truxima (rituximab-abbs)

Tysabri (natalizumab)

Xeljanz (tofacitinib)

Xeljanz XR (tofacitinib extended release)

Xolair (omalizumab)

Yuflyma (adalimumab-aaty)

Yusimry (adalimumab-aqvh)

ND Committee Review

Internal Medical Policy Committee 11-23-2021- Effective January 01, 2022

Adopted new policy to replace I-146-012 Monoclonal Antibodies for the Treatment of Eosinophilic Conditions,
New policy is for benralizumab (Fasenra) prefilled syringe, mepolizumab (Nucala) vial or reslizumab (Cinqair) as the benralizumab (Fasenra) autoinjector and mepolizumab (Nucala) autoinjector and prefilled syringe will be reviewed as pharmacy benefits.

Internal Medical Policy Committee 11-29-2022 - Effective January 01, 2023

Updated combination therapy criteria; and
Updated FDA approved and compendia supported criteria; and
Added additional Cinqair specific criteria; and
Removed FDA labeled contraindications criteria from the policy; and
Removed requested quantity (dose) is within FDA labeling for the requested indication criteria; and
Updated diagnosis codes for J2182; and
Added Agents NOT to be used Concomitantly list; and
Updated experimental/investigational statement

Internal Medical Policy Committee 9-12-2023 Effective October 01, 2023

Updated CRSwNP initial criteria
Updated Agents NOT to be used Concomitantly list

Internal Medical Policy Committee 9-17-2024 Effective November 01, 2024

Annual review no clinical content change

Internal Medical Policy Committee 11-19-2024 Effective December 08, 2024

Archived policy

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

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