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 17, 2024
Next Review:      December 20, 2025
 

Related MDC: NONE

Nucala® (mepolizumab)

Summary

Mepolizumab is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) for the add-on maintenance treatment of severe asthma patients aged 12 years and older and with an eosinophilic phenotype

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; January 2022. Accessed January 2022.

2. National Asthma Education and Prevention Program (NAEPP). Guidelines for the diagnosis and management of asthma. Expert Panel Report 3. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); August 2007.

3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2019 Update. Available from: http://www.ginasthma.org. Accessed September 2020.

4. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079.

5. Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on antineutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007; 66: 605-17.

6. Masi AT, Hunder GG, Lie JT; Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33(8):1094-100 (ISSN: 0004-3591).

7. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS Guidelines on Definition, Evaluation, and Treatment of Severe Asthma. Eur Respir J 2014; 43: 343-373.

8. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94. doi: 10.1136/annrheumdis-2016-209133.

9. Groh M, Panoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg– Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. European Journal of Internal Medicine 26 (2015) 545–553.

10. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020; 55: 1900588 [https://doi.org/10.1183/13993003.00588-2019]

11. Roufosse F, Kahn JE, 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 (2020), doi: https://doi.org/10.1016/j.jaci.2020.08.037.

12. National Asthma Education and Prevention Program (NAEPP). 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); December 2020.

13. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2021 Update. Available from: http://www.ginasthma.org. Accessed June 2021.

14. Han JK, Bachert C, Fokkens W, et al; SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet Respir Med. 2021 Apr 16:S2213-2600(21)00097-7. doi: 10.1016/S2213-2600(21)00097-7.

15. Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy. 2019;74:2312–2319. DOI: 10.1111/all.13875.

16. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.

Codes

Applicable Modifiers

Some modifiers.

Policy History