Mepolizumab (Nucala®)

We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

POLICY

INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications

Nucala is indicated for add-on maintenance treatment of patients with severe asthma aged 6 years and older, and with an eosinophilic phenotype.
Nucala is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).
Nucala is indicated for the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for ³6 months without an identifiable non-hematologic secondary cause.
Nucala is indicated for the add-on maintenance treatment of adult patients 18 years and older with chronic rhinosinusitis with nasal polyps (CRSwNP).
Nucala is indicated for the add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype.

Limitations of Use:

Not for relief of acute bronchospasm or status asthmaticus

All other indications are considered experimental/investigational and not medically necessary.

DOCUMENTATION

Submission of the following information is necessary to initiate the prior authorization review:

Asthma

Initial requests

Chart notes or medical record showing pretreatment blood eosinophil count, dependance on systemic corticosteroids if applicable.
Chart notes, medical record documentation, or claims history supporting previous medications tried including drug, dose, frequency, and duration.

Continuation requests

Chart notes or medical record documentation supporting improvement in asthma control.

EGPA

Initial requests

Chart notes or medical record showing pretreatment blood eosinophil count or percentage of blood eosinophil level (where applicable).
Chart notes, medical record documentation, or claims history supporting previous medications tried including drug, dose, frequency, and duration. If therapy is not advisable, documentation of clinical reason to avoid therapy.

Continuation requests

Chart notes or medical record documentation supporting beneficial response to treatment.

HES

Initial requests

FIP1L1-PDGFRA fusion gene test results.

Chart notes or medical record showing pretreatment blood eosinophil count.

Continuation requests

FIP1L1-PDGFRA fusion gene test results.
Chart notes or medical record documentation supporting improvement in HES control.

CRSwNP

Initial requests

Chart notes or medical record showing nasal endoscopy, anterior rhinoscopy, or computed tomography details (e.g., polyps location, size), Meltzer Clinical Score, or endoscopic nasal polyps score (NPS) (where applicable).
Chart notes, medical record documentation, or claims history supporting previous medications tried including drug, dose, frequency, and duration. If therapy is not advisable, documentation of clinical reason to avoid therapy.

Continuation requests

Chart notes or medical record documentation supporting positive clinical response.

COPD

Initial requests

Chart notes or medical record documentation demonstrating classic signs and/or symptoms of COPD (where applicable).
Chart notes, medical record documentation, or claims history of previous medications tried, including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy (where applicable).
Chart notes or medical record documentation showing absolute blood eosinophil count prior to initiating therapy with the requested medication (where applicable).
Chart notes or medical record documentation of moderate or severe exacerbations within the last year (where applicable).

Continuation requests

Chart notes or medical record documentation supporting positive clinical response.

EXCLUSIONS

Coverage will not be provided for treatment of HES for members with any of the following exclusions:

HES secondary to a non-hematologic cause (e.g., drug hypersensitivity, parasitic helminth infection, human immunodeficiency virus [HIV] infection, non-hematologic malignancy).
FIP1L1-PDGFRA kinase-positive HES.

PRESCRIBER SPECIALTIES

This medication must be prescribed by or in consultation with one of the following:

Asthma: allergist/immunologist or pulmonologist
Chronic rhinosinusitis with nasal polyposis: allergist/immunologist or otolaryngologist
Chronic obstructive pulmonary disease: pulmonologist or allergist/immunologist

COVERAGE CRITERIA

Asthma

Authorization of 6 months may be granted for members 6 years of age or older who have previously received a biologic drug (e.g., Dupixent, Cinqair) indicated for asthma in the past year.

Authorization of 6 months may be granted for treatment of severe asthma when all of the following criteria are met:

Member is 6 years of age or older.
Member meets either of the following criteria:

Member has a baseline blood eosinophil count of at least 150 cells per microliter.
Member is dependent on systemic corticosteroids.

Member has uncontrolled asthma as demonstrated by experiencing at least one of the following within the past year:

Two or more asthma exacerbations requiring oral or injectable corticosteroid treatment.
One or more asthma exacerbation(s) resulting in hospitalization or emergency medical care visit(s).
Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma).

Member has inadequate asthma control despite current treatment with both of the following medications at optimized doses:

High-dose inhaled corticosteroid.
Additional controller (i.e., long acting beta₂-agonist, long acting muscarinic antagonist, leukotriene modifier, or sustained-release theophylline).

Member will continue to use maintenance asthma treatments (i.e., inhaled corticosteroid and additional controller) in combination with the requested medication.

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Authorization of 12 months may be granted for members 18 years of age or older who have previously received a biologic drug (e.g., Fasenra) indicated for EGPA in the past year.

Authorization of 12 months may be granted for treatment of eosinophilic granulomatosis with polyangiitis when all of the following criteria are met:

Member is 18 years of age or older.
Member has a history or the presence of an eosinophil count of more than 1000 cells per microliter or a blood eosinophil level of greater than 10%.
Member is currently taking oral corticosteroids, unless contraindicated or not tolerated.

Member has at least two of the following disease characteristics of EGPA^:

Biopsy showing histopathological evidence of eosinophilic vasculitis, perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation
Neuropathy, mono or poly (motor deficit or nerve conduction abnormality)
Pulmonary infiltrates, non-fixed
Sino-nasal abnormality
Cardiomyopathy (established by echocardiography or magnetic resonance imaging)
Glomerulonephritis (hematuria, red cell casts, proteinuria)
Alveolar hemorrhage (by bronchoalveolar lavage)
Palpable purpura
Anti-neutrophil cytoplasmic anti-body (ANCA) positive (Myeloperoxidase or proteinase 3)

Member has had at least one relapse (i.e., requiring increase in oral corticosteroids dose, initiation/increased dose of immunosuppressive therapy or hospitalization) within 2 years prior to starting treatment with the requested medication or has refractory disease.

Hypereosinophilic Syndrome (HES)

Authorization of 12 months may be granted for treatment of HES when all of the following criteria are met:

Member is 12 years of age or older.
Member has a history or presence of a blood eosinophil count of at least 1000 cells per microliter.
Member will not use the requested medication as monotherapy.
Member has been on a stable dose of HES therapy (e.g., oral corticosteroid, immunosuppressive, and/or cytotoxic therapy).
Member has had HES for at least 6 months.
Member has experienced at least two HES flares within the past 12 months.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Authorization of 6 months may be granted for members 18 years of age or older who have previously received a biologic drug (e.g., Dupixent, Xolair) indicated for CRSwNP in the past year.

Authorization of 6 months may be granted for treatment of chronic rhinosinusitis with nasal polyps when all of the following criteria are met:

Member is 18 years of age or older.
Member has bilateral nasal polyposis and chronic symptoms of sinusitis despite intranasal corticosteroid treatment for at least 4 weeks unless contraindicated or not tolerated.
The member has CRSwNP despite one of the following:

Prior sino-nasal surgery.
Prior treatment with systemic corticosteroids within the last two years was ineffective, unless contraindicated or not tolerated.

Member has one of the following:

A bilateral nasal endoscopy, anterior rhinoscopy, or computed tomography (CT) showing polyps reaching below the lower border of the middle turbinate or beyond in each nostril.
Meltzer Clinical Score of 2 or higher in both nostrils.
A total endoscopic nasal polyp score (NPS) of at least 5 with a minimum score of 2 for each nostril.

Member has symptoms of nasal blockage, congestion, or obstruction plus one of the following additional symptoms:

Rhinorrhea (anterior/posterior).
Reduction or loss of smell.
Facial pain or pressure.

Member will continue to use a daily intranasal corticosteroid while being treated with the requested medication, unless contraindicated or not tolerated.

Chronic Obstructive Pulmonary Disease (COPD)

Authorization of 12 months may be granted for members 18 years of age or older who have previously received a biologic drug (e.g., Dupixent) indicated for COPD in the past year.

Authorization of 12 months may be granted for treatment of COPD in members when all of the following criteria are met:

Member is 18 years of age or older.
Diagnosis has been confirmed by spirometry showing forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) less than 0.7 post-bronchodilation.
Member demonstrates classic signs or symptoms of COPD (e.g., dyspnea, wheezing, chest tightness, fatigue, activity limitation, cough with or without sputum production, chronic bronchitis).
Member has an absolute blood eosinophil count of at least 150 cells per microliter prior to initiating therapy with the requested medication.
Member has inadequately controlled COPD as demonstrated by experiencing either of the following in the last year:

At least two moderate exacerbations resulting in treatment with systemic glucocorticoids, antibiotics, or both.
One or more severe exacerbation(s) requiring hospitalization or an emergency medical care visit.

Member meets either of the following:
- Member is currently receiving maintenance inhaled triple therapy (i.e., inhaled corticosteroid [ICS], long-acting muscarinic antagonist [LAMA], and long-acting beta2-agonist [LABA]).
- Member is currently receiving a LAMA and LABA, and has a contraindication to ICS.
Member will continue to use maintenance COPD treatments (e.g., ICS with LAMA and LABA, LAMA and LABA) in combination with the requested medication.

CONTINUATION OF THERAPY

Asthma

Authorization of 12 months may be granted for continuation of treatment of severe asthma when all of the following criteria are met:

Member is 6 years of age or older.
Asthma control has improved on the requested medication as demonstrated by at least one of the following:

A reduction in the frequency and/or severity of symptoms and exacerbations.
A reduction in the daily maintenance oral corticosteroid dose.

Member will continue to use maintenance asthma treatments ( i.e., inhaled corticosteroid and additional controller) in combination with the requested medication.

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Authorization of 12 months may be granted for continuation of treatment of eosinophilic granulomatosis with polyangiitis when all of the following criteria are met:

Member is 18 years of age or older.
Member has beneficial response to treatment with the requested medication as demonstrated by any of the following:

A reduction in the frequency of relapses.
A reduction or discontinuance of daily oral corticosteroid dose.
No active vasculitis.

Hypereosinophilic Syndrome (HES)

Authorization of 12 months may be granted for continuation of treatment of HES when both of the following criteria are met:

Member is 12 years of age or older.
Member has experienced a reduction in HES flares since starting treatment with the requested medication.

Chronic Rhinosinusitis with Nasal Polyps

Authorization of 12 months may be granted for continuation of treatment of chronic rhinosinusitis with nasal polyposis when all of the following are met:

Member is 18 years of age or older.
Member has achieved or maintained a positive clinical response with the requested medication as evidenced by improvement in signs and symptoms of CRSwNP (e.g., improvement in nasal congestion, nasal polyp size, loss of smell, anterior or posterior rhinorrhea, sinonasal inflammation, hyposmia and/or facial pressure or pain or reduction in corticosteroid use).
Member will continue to use a daily intranasal corticosteroid while being treated with the requested medication, unless contraindicated or not tolerated.

Chronic Obstructive Pulmonary Disease (COPD)

Authorization of 12 months may be granted for continuation of treatment of COPD when all of the following criteria are met:

Members is 18 years of age or older.
Member has achieved or maintained a positive clinical response as evidenced by improvement in signs and symptoms of COPD (e.g., decrease in exacerbations, improvement in pre-bronchodilator FEV₁) or stabilization of disease.
Member will continue to use maintenance COPD treatments (e.g., ICS with LAMA and LABA, LAMA and LABA) in combination with the requested medication.

OTHER

For all indications: Member cannot use the requested medication concomitantly with any other biologic drug or targeted synthetic drug for the same indication.

Note: If the member is a current smoker or vaper, they should be counseled on the harmful effects of smoking and vaping on pulmonary conditions and available smoking and vaping cessation options.

MEDICATION QUANTITY LIMITS

Drug Name	Diagnosis	Maximum Dosing Regimen
Nucala (Mepolizumab)	Asthma	Route of Administration: Subcutaneous 6-11 Years 40mg every 4 weeks ≥12 Years 100mg every 4 weeks
Nucala (Mepolizumab)	Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)	Route of Administration: Subcutaneous ≥18 Years 100mg every 4 weeks
Nucala (Mepolizumab)	Eosinophilic Granulomatosis With Polyangiitis (EGPA)	Route of Administration: Subcutaneous ≥18 Years 300mg every 4 weeks as 3 separate 100-mg injections
Nucala (Mepolizumab)	Hypereosinophilic Syndrome (HES)	Route of Administration: Subcutaneous ≥12 Years 300mg every 4 weeks as 3 separate 100-mg injections

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

Nucala [package insert]. Durham, NC: GlaxoSmithKline; May 2025.
Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207.
Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-1197.
National Institutes of Health. National Asthma Education and Prevention Program Expert Panel Report 3: Asthma Management Guidelines: Focused Updates 2020. Bethesda, MD: National Heart Lung and Blood Institute; December 2020. Available at: https://www.nhlbi.nih.gov/sites/default/files/publications/AsthmaManagementGuidelinesReport-2-4-21.pdf. Accessed March 1, 2025.
Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2024 update. Available at: https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024- Strategy-Report-24_05_22_ WMS.pdf. Accessed March 1, 2025.
Kew KM, Karner C, Mindus SM. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children (review). Cochrane Database Syst Rev. 2013;12:CD009019.
American Academy of Allergy, Asthma & Immunology (AAAAI) 2020 Virtual Annual Meeting. Available at: https://annualmeeting.aaaai.org/. Accessed March 8, 2025.
Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017:18;376(20):1921-1932.
GlaxoSmithKline. A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis. Available from https://clinicaltrials.gov/ct2/show/record/NCT02020889. NLM identifier: NCT02020889. Accessed March 14, 2025.
Groh M, Pagnoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss) (EGPA) Consensus Task Force Recommendations for evaluation and management. Eur J Intern Med. 2015;26(7):545-553.
Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47.
Shomali W, Gotlib J. World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. 2024 May;99(5):946-968.
Butt NM, Lambert J, Ali S, et al. Guideline for the investigation and management of eosinophilia. Br J Haematol. 2017;176(4):553-572.
Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141-1153.
Bachert C, Han JK, Wagenmann M, et al, EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management. J Allergy Clin Immunol. 2021;147(1):29-36.
Cloutier MM, Dixon AE, Krishnan JA, et al. Managing asthma in adolescents and adults: 2020 asthma guideline update from the National Asthma Education and Prevention Program. JAMA. 2020;324(22): 2301-2317.
American College of Rheumatology. 2021 American college of rheumatology/vasculitis foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis & Rheumatology. https://vasculitisfoundation.org/wp-content/uploads/2024/01/2021-ACR-VF-Guideline-for-Management-of-ANCA-Associated-Vasculitis.pdf. Accessed March 16, 2025.
Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl S29):1-464.
Hopkins C. Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med. 2019;381(1):55-63.
Rank MA, Chu DK, Bognanni A, et al. The Joint Task Force 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.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2024 Report). Available at: https://goldcopd.org/2024-gold-report/. Accessed May 30, 2025.
ClinicalTrials.gov. National Library of Medicine (US). Identifier NCT04133909. Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE). Last updated December 11, 2024. Accessed 2025 June 2. Available from: https://clinicaltrials.gov/study/NCT04133909.
ClinicalTrials.gov. National Library of Medicine (US). Identifier NCT02105948. Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients. Last updated August 31, 2018. Accessed 2025 June 2. Available from: https://clinicaltrials.gov/study/NCT02105948.

ORIGINAL EFFECTIVE DATE: 12/1/2015

MOST RECENT REVIEW DATE: 12/2/2025

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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