State and School Employees' Health Insurance Plan - Interleukin-5 Antagonist Monoclonal Antibodies

POLICY NUMBER

S.5.01.499

Cinqair (reslizumab)

Fasenra (benralizumab)

Nucala (mepolizumab)

Please perform a search of the State Health Plan Medical Drug Formulary for drugs administered and billed through the medical setting.

DESCRIPTION

Cinqair

Cinqair (reslizumab) is an interleukin-5 antagonist monoclonal antibody (IgG4 kappa) indicated for patients 18 years and older for add-on maintenance treatment of severe asthma with an eosinophilic phenotype. Cinqair is not for relief of acute bronchospasm or status asthmaticus or treatment of other eosinophilic conditions.

Fasenra

Fasenra (benralizumab) is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) indicated for add-on maintenance treatment of patients with severe asthma aged 12 years and older with an eosinophilic phenotype and for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Fasenra is not indicated for relief of acute bronchospasm or status asthmaticus.

Nucala

Nucala (mepolizumab) is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) indicated for add-on maintenance treatment of patients 6 years of age and older with severe asthma with an eosinophilic phenotype, for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), for the 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, and for the add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids. Nucala is not for relief of acute bronchospasm or status asthmaticus. 

Related medical policies - 

• State and School Employees’ Health Insurance Plan - Xolair (omalizumab)

POLICY

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Criteria

Cinqair (reslizumab) or Nucala (mepolizumab) may be considered medically necessary when ALLof the following criteria are met:

1. ONE of the following:

   1. The individual is 18 years of age or older;

   2. The individual is 12 years of age or older, and the request is for Nucala (mepolizumab) for treatment of hypereosinophilic syndrome; OR

   3. The individual is 6 years of age or older, and the request is for Nucala (mepolizumab) for treatment of severe eosinophilic asthma;

2. ONE of the following:

   1. The individual has a documented 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 request is for Cinqair (reslizumab), and the individual has a baseline eosinophilic blood count ≥400 cells/microliter within the previous 30 days; OR

         2. The request is for Nucala (mepolizumab) and ONE of the following:

            1. The individual has a baseline (prior to therapy with the requested agent) blood eosinophilic count ≥150 cells/microliter while on high-dose inhaled corticosteroids or daily oral corticosteroids;

            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% while on high-dose inhaled corticosteroids or daily oral corticosteroids;

      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;

         2. Serious asthma exacerbations requiring hospitalization, mechanical ventilation, or visit to the emergency room or urgent care within the past 12 months;

         3. Controlled asthma that worsens when the doses of inhaled or systemic corticosteroids are tapered; OR

         4. The individual has baseline (prior to therapy with the requested agent) Forced Expiratory Volume (FEV1) <80% of predicted;

      3. ONE of the following:

         1. BOTH of the following:

            1. The individual is currently treated with a maximally tolerated inhaled corticosteroid (ICS) for at least 3 months and has been adherent for 90 days within the past 120 days; AND

            2. The individual 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. Long-acting beta-2 agonist (LABA);

               2. Leukotriene receptor antagonist (LTRA);

               3. Long-acting muscarinic antagonist (LAMA); OR

               4. Theophylline; OR

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to inhaled corticosteroids, LABA, LTRA, LAMA, AND theophylline; AND

      4. The individual will continue asthma control therapy (e.g., ICS, ICS/LABA, LTRA, LAMA, theophylline) in combination with the requested agent;

   2. The individual has a documented diagnosis of eosinophilic granulomatosis with polyangiitis (EPGA) and ALL of the following:

      1. The request is for Nucala (mepolizumab);

      2. The individual has had a diagnosis of EGPA for at least 6 months with a history of relapsing or refractory disease;

      3. ONE of the following:

         1. The individual has a baseline (prior to therapy for the requested indication) blood eosinophilia greater than or equal to 1000 cells/microliter; OR

         2. The individual 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;

      4. The individual has a history or presence of asthma;

      5. The individual 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

      6. ONE of the following:

         1. BOTH of the following:

            1. The individual is currently on maximally tolerated oral corticosteroid therapy for at least 4 weeks; AND

            2. The individual will be using oral corticosteroid therapy in combination with the requested agent; OR

         2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to oral corticosteroids therapy;

   3. The individual has a documented diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) and ALL of the following:

      1. The request is for Nucala (mepolizumab);

      2. The individual’s diagnosis of CRSwNP was confirmedusing ONE of the following:

         1. Anterior rhinoscopy or endoscopy; OR

         2. Sinus CT scan;

      3. The individual has at least TWO of the following symptoms consistent with chronic rhinosinusitis:

         1. Nasal discharge (rhinorrhea or post-nasal drainage);

         2. Nasal obstruction or congestion;

         3. Loss or decreased sense of smell (hyposmia); OR

         4. Facial pressure or pain;

      4. The individual has had symptoms consistent with chronic rhinosinusitis for at least 12 consecutive weeks;

      5. ONE of the following:

         1. The individual has tried and had an inadequate response to continuous treatment with an intranasal corticosteroid (e.g., fluticasone nasal spray, mometasone nasal spray) after at least a 4-week duration of therapy; OR

         2. The individual has a documented intolerance, hypersensitivity, or FDA-labeled contraindication to ALL intranasal corticosteroids; AND

      6. The individual is currently treated with standard nasal polyp maintenance therapy (e.g., nasal saline irrigation, intranasal corticosteroids) and will continue to use a standard nasal polyp maintenance therapy in combination with the requested agent; OR

   4. The individual has a diagnosis of hypereosinophilic syndrome (HES) and ALL of the following:

      1. The request is for Nucala (mepolizumab);

      2. The individual has had a diagnosis of HES for at least 6 months;

      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 1000 cells/mL;

            2. The individual has a percentage of eosinophils in bone marrow section exceeding 20% of all nucleated cells;

            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 [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]);

            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

            3. The individual does NOT have FIP1L1-PDGFRA-positive disease;

      4. The individual 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);

      5. ONE of the following:

         1. The individual has tried and had an inadequate response to ONE of the following:

            1. Oral corticosteroid (OCS) therapy; OR

            2. Non-corticosteroid immunosuppressive agent (e.g., cyclosporine, hydroxyurea, methotrexate); OR

         2. The individual has an intolerance, hypersensitivity, or FDA-labeled contraindication to ALL oral corticosteroids and non-corticosteroid immunosuppressive agents; AND

      6. The individual will continue existing HES maintenance therapy (e.g., oral corticosteroid and/or hydroxyurea, etc.) in combination with the requested agent;

3. The prescriber is a specialist in the area of the individual’s diagnosis or has consulted with a specialist in the area of the individual’s diagnosis (e.g., pulmonologist, otolaryngologist, allergist, immunologist);

4. The individual does not have any FDA labeled contraindications to the requested agent;

5. The individual is not currently being treated with another immunomodulatory agent (i.e., TNF-inhibitor, IL-inhibitor, anti-IgE antibody, JAK inhibitor etc.);

6. If the request is for Nucala vials to be administered by a healthcare professional, the individual has tried unsuccessfully to utilize self-administered Nucala or is clinically unable to do so; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 6 months

Renewal Criteria

Cinqair (reslizumab) or Nucala (mepolizumab) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has been previously approved for therapy with the requested agent through BCBSMS review process;

2. ONE of the following:

   1. 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 as indicated by ONE of the following:

         1. Increase in percent predicted FEV1 from baseline;

         2. Decrease in the dose of inhaled corticosteroids required to control the individual’s asthma;

         3. Decrease in need for treatment with systemic corticosteroids due to exacerbations of asthma; OR

         4. Decrease in number of hospitalizations or visits to urgent care or emergency room due to exacerbation of asthma; AND

      2. The individual is currently treated within the past 90 days 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);

   2. The individual has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and BOTH of the following:

      1. The requested agent is Nucala; AND

      2. The individual has had improvements or stabilization with the requested agent from baseline as indicated by ONE of the following:

         1. Remission achieved with the requested agent;

         2. Decrease in oral corticosteroid maintenance dose required for control of EGPA symptoms;

         3. Decrease in hospitalization due to symptoms of EGPA; OR

         4. Dose of maintenance corticosteroid therapy and/or immunosuppressant therapy was not increased;

   3. The individual has a diagnosis of chronic rhinosinusitis with nasal polyposis (CRSwNP) and ALL of the following:

      1. The requested agent is Nucala;

      2. The individual has had clinical benefit with the requested agent (e.g., reduction in nasal congestion, nasal polyp size, rhinorrhea, sinonasal inflammation, improved sense of smell); 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 

   4. The individual has a diagnosis of hypereosinophilic syndrome (HES) and ALL of the following:

      1. The requested agent is Nucala;

      2. The individual has had improvements or stabilization with the requested agent from baseline 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. The individual will continue existing HES therapy (e.g., OCS, hydroxyurea, etc.) in combination with the requested agent;

3. The prescriber is a specialist in the area of the individual’s diagnosis or has consulted with a specialist in the area of the individual’s diagnosis (e.g., pulmonologist, otolaryngologist, allergist, immunologist);

4. The individual does not have an FDA labeled contraindication to therapy with the requested agent;

5. The individual is not currently being treated with another immunomodulatory agent (i.e., TNF-inhibitor, IL-inhibitor, anti-IgE antibody, JAK inhibitor, etc.);

6. If the request is for Nucala vials to be administered by a healthcare professional, the individual has tried unsuccessfully to utilize self-administered Nucala or is clinically unable to do so; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months

Fasenra (benralizumab) is considered not medically necessary as there are other formulary alternatives covered by the plan as add-on therapy for the treatment of asthma.

Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees): Self-administered drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a self-administered drug are not covered under the medical benefit.

POLICY GUIDELINES

Medical Policy Manual coverage guidelines should not be used in lieu of the Participant's specific benefit plan language outlined in the Mississippi's State and School Employees’ Life and Health Insurance Plan.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Participant's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Participant's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Participant, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to the Participant. When applied to the care of an Inpatient, it further means that services for the Participant's medical symptoms or conditions require that the services cannot be safely provided to the Participant as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses (for >3 months use) as appropriate for the disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure or lack of response for the purpose of this review.

BCBSMS determines member medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

07/01/2023: New policy added.

06/03/2025: Policy reviewed by Pharmacy & Therapeutics (P&T) Committee; no changes.

10/01/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Fasenra (benralizumab) and Nucala (mepolizumab). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Initial and renewal criteria revised regarding age criteria, individuals with a documented diagnosis of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis (EPGA), chronic rhinosinusitis with nasal polyps (CRSwNP), and hypereosinophilic syndrome (HES), and regarding administration of Nucala. Sources updated.

SOURCE(S)

1. Cinqair prescribing information. Teva Respiratory. June 2020. Last accessed March 2025.

2. Fasenra prescribing information. AstraZeneca Pharmaceuticals LP. September 2024. Last accessed March 2025.

3. Nucala prescribing information. GlaxoSmithKline LLC. March 2023. Last accessed March 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Not Medically Necessary Codes

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