Medical Drug Criteria (MDC)

Policy Num:       P1.002.004
Policy Name:     Nucala® (mepolizumab)
Policy ID:          [P1.002.004]  [Ac / Mg / M+ / P+]  [0.00.00]

Last Review:       December 16, 2025
Next Review:      December 20, 2026
 

Related MDC: NONE

Nucala® (mepolizumab)

Summary

Nucala (mepolizumab) is an interleukin-5 receptor antagonist indicated for add-on maintenance treatment of patients aged 6 years and older with severe asthma and with an eosinophilic phenotype, for add-on maintenance treatment of adult patients 18 years and older with chronic rhinosinusitis with nasal polyps (CRSwNP), the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), for add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, and 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.

POLICY STATEMENTS

Coverage is provided in the following conditions:

Universal Criteria  

 Must not be used in combination with another anti-IgE, anti-IL4, or anti-IL5 monoclonal antibody (e.g., benralizumab, omalizumab, reslizumab, dupilumab, etc.); AND

Severe Asthma

 Patient is at least 6 years of age; AND

 Patient must have severe* disease; AND

 Patient must have asthma with an eosinophilic phenotype defined as blood eosinophils ≥300 cells/µL within previous 12 months or ≥150 cells/µL within 6 weeks of dosing OR the patient is dependent on systemic corticosteroids; AND

 Must be used for add-on maintenance treatment in patients regularly receiving BOTH of the following:

o Medium to high-dose inhaled corticosteroids; AND

o An additional controller medication (e.g., long-acting beta agonist, leukotriene modifiers, etc.); AND

 Will not be used for treatment of acute bronchospasm or status asthmaticus; AND

 Patient must have two or more exacerbations in the previous year requiring daily oral corticosteroids for at least 3 days (in addition to the regular maintenance therapy defined above); AND

 Baseline measurement of at least one of the following for assessment of clinical status:

o Use of systemic corticosteroids

o Use of inhaled corticosteroids

o Number of hospitalizations, ER visits, or unscheduled visits to healthcare provider due to condition

o Forced expiratory volume in 1 second (FEV1)

Eosinophilic Granulomatosis with Polyangiitis (EGPA)/Churg-Strauss Syndrome

 Patient is at least 18 years of age; AND

 Patient has a confirmed diagnosis of EGPA§ (aka Churg-Strauss Syndrome); AND

 Patient must have blood eosinophils ≥150 cells/µL within 6 weeks of dosing; AND

 Patient has been on stable doses of concomitant oral corticosteroid therapy for at least 4 weeks (i.e., prednisone or prednisolone at a dose of 7.5 mg/day); AND

 Physician has assessed baseline disease severity utilizing an objective measure/tool (e.g., Birmingham Vasculitis Activity Score [BVAS], history of asthma symptoms and/or exacerbations, duration of remission, or rate of relapses, etc.)

Hypereosinophilic Syndrome (HES)

 Patient is at least 12 years of age; AND

 Patient has been diagnosed with HES for at least 6 months prior to starting treatment; AND

 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

 Patient has a history of 2 or more HES flares within the previous 12 months (e.g., documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in therapy); AND

 Patient must have blood eosinophils ≥1000 cells/µL within 4 weeks of dosing; AND

 Used in combination with stable doses of at least one other HES therapy (e.g., oral corticosteroids, immunosuppressive agents, cytotoxic therapy, etc.)

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

 Patient is at least 18 years of age; AND

 Patient has bilateral symptomatic sino-nasal polyposis with symptoms lasting at least 8 weeks; AND

 Patient has failed on at least 8 weeks of intranasal corticosteroid therapy; AND

 Patient has at least four (4) of the following indicators for biologic treatment [Note: Patients with a history of sino-nasal surgery are only required to have at least three (3) of the indicators]:

o Patient has evidence of type 2 inflammation (i.e., biological biomarkers indicating immune dysregulation and epithelial barrier dysfunction)

o Patient has required two or more short courses of systemic corticosteroids within the previous year o Disease significantly impairs the patient’s quality of life o Patient has experienced significant loss of smell o Patient has a comorbid diagnosis of asthma; AND

 Patient does not have any of the following:

o Antrochoanal polyps o Nasal septal deviation that would occlude at least one nostril

o Disease with lack of signs of type 2 inflammation o Cystic fibrosis o Mucoceles; AND

 Other causes of nasal congestion/obstruction have been ruled out (e.g., acute sinusitis, nasal infection or upper respiratory infection, rhinitis medicamentosa, tumors, infections, granulomatosis, etc.); AND

 Physician has assessed baseline disease severity utilizing an objective measure/tool; AND

 Therapy will be used in combination with intranasal corticosteroids unless not able to tolerate or is contraindicated

POLICY GUIDELINES

Renewal Criteria

 Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND

 Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: parasitic (helminth) infection, herpes zoster infection, severe hypersensitivity reactions, etc.; AND

Severe Asthma

 Improvement in asthma symptoms or asthma exacerbations as evidenced by decrease in one or more of the following:

 Use of systemic corticosteroids

 Two-fold or greater decrease in inhaled corticosteroid use for at least 3 days

 Hospitalizations

 ER visits

 Unscheduled visits to healthcare provider; OR

 Improvement from baseline in forced expiratory volume in 1 second (FEV1)

Eosinophilic Granulomatosis with Polyangiitis/Churg-Strauss Syndrome

 Disease response as indicated by improvement in signs and symptoms compared to baseline as evidenced in one or more of the following:

 Patient is in remission [defined as a Birmingham Vasculitis Activity Score (BVAS) score=0 and a prednisone/prednisolone daily dose of ≤ 7.5 mg]

 Decrease in maintenance dose of systemic corticosteroids

 Improvement in BVAS score compared to baseline

 Improvement in asthma symptoms or asthma exacerbations

 Improvement in duration of remission or decrease in the rate of relapses

Hypereosinophilic Syndrome (HES)

 Disease response as indicated by a decrease in HES flares from baseline (Note: An HES flare is defined as worsening of clinical signs and symptoms of HES or increasing eosinophils (on at least 2 occasions), resulting in the need to increase oral corticosteroids or increase/add cytotoxic or immunosuppressive HES therapy)

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) 

 Disease response as indicated by improvement in signs and symptoms compared to baseline in one or more of the following: nasal/obstruction symptoms, improvement of sinus opacifications as assessed by CT-scans and/or an improvement on a disease activity scoring tool [e.g., nasal polyposis score (NPS), nasal congestion (NC) symptom severity score, sinonasal outcome test-22 (SNOT-22), etc.]; OR

 Patient had an improvement in at least one (1) of the following response criteria:

 Reduction in nasal polyp size

 Reduction in need for systemic corticosteroids

 Improvement in quality of life

 Improvement in sense of smell

 Reduction of impact of comorbidities

DOSAGE/ADMINISTRATION

Severe Asthma with Eosinophilic Phenotype

Pediatric Patients Aged 6 to 11 years (100 mg single-dose vial 
or 40 mg/0.4 mL single-dose prefilled syringe ONLY)§: 
40 mg administered subcutaneously once every 4 weeks 
Adults and Adolescents Aged 12 years and older: 
100 mg administered subcutaneously once every 4 weeks
 

Eosinophilic Granulomatosis with Polyangiitis/Churg-Strauss Syndrome 

300 mg administered subcutaneously once every 4 weeks as 3 
separate 100-mg injections. Administer each injection at least 
2 inches apart. 

Hypereosinophilic Syndrome (HES) 

300 mg administered subcutaneously once every 4 weeks as 3 
separate 100-mg injections. Administer each injection at least 
2 inches apart.

 
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) 

100 mg administered subcutaneously once every 4 weeks. 

REQUIRED MEDICAL INFORMATION

Baseline measurement of at least one of the following for assessment of clinical status:

o Use of systemic corticosteroids

o Use of inhaled corticosteroids

o Number of hospitalizations, ER visits, or unscheduled visits to healthcare provider due to condition

o Forced expiratory volume in 1 second (FEV1)

EXCLUSION CRITERIA

None

BENEFIT APPLICATION

As stated in the policy.

OTHER CRITERIA

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

References

1. Nucala® [package insert]. Philadelphia, PA: GlaxoSmithKline, LLC; May 2025.
2. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb:43(2):343-73.
3. Institute for Clinical and Economic Review (ICER). Mepolizumab (Nucala®, GlaxoSmithKline plc.) for the Treatment of Severe Asthma with Eosinophilia: Effectiveness, Value, and ValueBased Price Benchmarks. March 14, 2016. Available at http://icer-review.org/material/asthmafinal-report/. Accessed May 2024.
4. Global Initiative for Asthma. Difficult-To-Treat & Severe Asthma in adolescent and adult patients. Diagnosis and Management, 2024. Available at http://www.ginasthma.org. Accessed May 29, 2025.
5. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, et al. Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. New Eng J Med. 2014 Sept:371(13):1189-97.
6. Parameswaran KN, Dasgupta A, et al. Mepolizumab in COPD with Eosinophilic Bronchitis: A Randomized Clinical Trial. Poster session presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology, Los Angeles, CA. March 2016.
7. Centers for Disease Control and Prevention. Asthma. Available at http://www.cdc.gov./asthma/. Accessed May 29, 2025.
8. National Heart, Lung and Blood Institute. Explore Asthma. Available at http://www.nhlbi.nih.gov. Accessed May 29, 2025.
9. Hypereosinophilic Syndrome (HES). American Academy of Allergy, Asthma & Immunology. Available at https://www.aaaai.org. Accessed May 29, 2025. 

10. Roufosse F, Kahn J-E, Rothenberg ME, et. al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a Phase III, randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology. September 2020.
11. Roufosse F, Klion A, Weller P. Hypereosinophilic syndromes: Treatment. Updated November 30, 2022. Accessed May 29, 2025.
12. Peters AT, Spector S, Hsu J, et al. Diagnosis and management of rhinosinusitis: a practice parameter update. Ann Allergy Asthma Immuno. 2014;113:347-385.
13. Han JK, Bachert C, Fokkens W, et al.SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled,
phase 3 trial. Lancet Respir Med. 2021 Apr 16:S2213-2600(21)00097-7. doi: 10.1016/S2213- 2600(21)00097-7. Epub ahead of print.
14. Buchheit KM, Holbrook EH. Chronic rhinosinusitis with nasal polyposis: Management and prognosis. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Updated April 24, 2025. Accessed on May 29, 2025.
15. Holguin F, Cardet JC, Chung KF, et al.. Management of severe asthma: a European RespiratorySociety/American Thoracic Society guideline. Eur Respir J. 2020 Jan 2;55(1):1900588. doi: 10.1183/13993003.00588-2019

Codes

Applicable Modifiers

Some modifiers.

Policy History