FASENRA, Benralizumab Form

Benralizumab (Fasenra®) is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1 kappa). FDA Approved Indication(s) Fasenra is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Limitation(s) of use:
• Fasenra is not indicated for treatment of other eosinophilic conditions.
• Fasenra is not indicated for the relief of acute bronchospasm or status asthmaticus. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Fasenra is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Severe Asthma (must meet all):

1. Diagnosis of asthma;
   2. Member has an absolute blood eosinophil count ≥ 150 cells/mcL within the past 3 months;
2. Prescribed by or in consultation with a pulmonologist, immunologist, or allergist;
   4. Age ≥ 12 years;
   5. Member has experienced ≥ 2 exacerbations within the last 12 months, requiring any of the following despite adherent use of controller therapy (i.e., medium- to high-dose inhaled corticosteroid [ICS] plus either a long-acting beta2 agonist [LABA] or leukotriene modifier [LTRA] if LABA contraindication/intolerance): a. Oral/systemic corticosteroid treatment (or increase in dose if already on oral corticosteroid);
      b. Urgent care visit or hospital admission; c. Intubation;

3. Fasenra is prescribed concurrently with an ICS plus either a LABA or LTRA;

   7. Fasenra is not prescribed concurrently with Cinqair®, Nucala®, Dupixent®, Xolair®, or Tezspire®; Page 1 of 8

   CLINICAL POLICY Benralizumab

4. Dose does not exceed 30 mg every 4 weeks for the first 3 doses, then 30 mg every 8 weeks thereafter. Approval duration: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):
5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Severe Asthma (must meet all):
7. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
8. Demonstrated adherence to asthma controller therapy (an ICS plus either a LABA or LTRA) as evidenced by proportion of days covered (PDC) of 0.8 in the last 6 months (i.e., member has received asthma controller therapy for at least 5 of the last 6 months);
9. Member is responding positively to therapy (examples may include but are not limited to: reduction in exacerbations or corticosteroid dose, improvement in forced expiratory volume over one second since baseline, reduction in the use of rescue therapy);
10. Fasenra is not prescribed concurrently with Cinqair, Nucala, Dupixent, Xolair, or Tezspire;

11. If request is for a dose increase, new dose does not exceed 30 mg every 8 weeks.
    Approval duration:
    Medicaid/HIM – 12 months
    Commercial – 6 months or member’s renewal period, whichever is longer Page 2 of 8

    CLINICAL POLICY Benralizumab B. Other diagnoses/indications (must meet 1 or 2):

12. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

13. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Acute bronchospasm or status asthmaticus. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration BEC: blood eosinophil count GINA: Global Initiative for Asthma ICS: inhaled corticosteroid LABA: long-acting beta2 agonist
    LTRA: leukotriene modifier
    PDC: proportion of days covered Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose ICS (medium – high dose) Qvar (beclomethasone) > 200 mcg/day 4 actuations BID 40 mcg, 80 mcg per actuation 1-4 actuations BID budesonide (Pulmicort) > 400 mcg/day 2 actuations BID Alvesco (ciclesonide) 90 mcg, 180 mcg per actuation 2-4 actuations BID

    160 mcg/day 2 actuations BID Page 3 of 8

    CLINICAL POLICY Benralizumab Drug Name Dosing Regimen Flovent (fluticasone propionate) 80 mcg, 160 mcg per actuation 1-2 actuations BID

    250 mcg/day 44-250 mcg per actuation 2-4 actuations BID 200 mcg/day
    100 mcg, 200 mcg per actuation 1 actuation QD Asmanex (mometasone) > 200 mcg/day Arnuity Ellipta (fluticasone furoate) HFA: 100 mcg, 200 mcg per actuation Twisthaler: 110 mcg, 220 mcg per actuation 1-2 actuations QD to BID LABA Serevent (salmeterol) 50 mcg per dose 1 inhalation BID Combination products (ICS + LABA) Dulera (mometasone/ formoterol) Breo Ellipta (fluticasone/vilanterol) Advair (fluticasone/ salmeterol) 100/5 mcg, 200/5 mcg per actuation 2 actuations BID 100/25 mcg, 200/25 mcg per actuation 1 actuation QD Diskus: 100/50 mcg, 250/50 mcg, 500/50 mcg per actuation HFA: 45/21 mcg, 115/21 mcg, 230/21 mcg per actuation 1 actuation BID 55/13 mcg, 113/14 mcg, 232/14 mcg per actuation 1 actuation BID 80 mcg/4.5 mcg, 160 mcg/4.5 mcg per actuation 2 actuations BID fluticasone/salmeterol (Airduo RespiClick®) Symbicort (budesonide/ formoterol)
    LTRA montelukast (Singulair) 4 to 10 mg PO QD zafirlukast (Accolate) zileuton ER (Zyflo CR) Zyflo (zileuton) Oral corticosteroids dexamethasone (Decadron) methylprednisolone (Medrol) 10 to 20 mg PO BID 1,200 mg PO BID 600 mg PO QID 0.75 to 9 mg/day PO in 2 to 4 divided doses 40 to 80 mg PO in 1 to 2 divided doses Varies Varies Dose Limit/ Maximum Dose 2 actuations BID 1 actuation QD 2 inhalations BID 1 inhalation BID 4 actuations per day 1 actuation QD 1 actuation BID 1 actuation BID 2 actuations BID 10 mg per day 40 mg per day 2,400 mg per day 2,400 mg per day Page 4 of 8

    CLINICAL POLICY Benralizumab Drug Name Dosing Regimen Dose Limit/ Maximum Dose 40 to 80 mg PO in 1 to 2 divided doses Varies prednisolone (Millipred, Orapred ODT) prednisone (Deltasone) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 40 to 80 mg PO in 1 to 2 divided doses Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity • Boxed warning(s): none reported Appendix D: General Information
    • The pivotal trials defined severe asthma as 2 or more exacerbations of asthma despite regular use of high-dose ICS plus an additional controller (e.g., LABA or LTRA) with or without oral corticosteroids. Although the CALIMA trial included patients receiving medium-dose ICS, Fasenra was not shown to have an effect on annual exacerbation rate, pre-bronchodilator forced expiratory volume in 1 second, or total asthma symptom score in those patients. • Clinically significant exacerbation was defined as a worsening of asthma (any new or increased symptoms or signs that were concerning) that led to one of the following: (1) use of systemic corticosteroids, (2) emergency department or visit to urgent care center, or (3) inpatient hospital stay. • Baseline blood eosinophil count (BEC) is a predictor of response to therapy. Although the SIROCCO and CALIMA trials were powered for efficacy analysis in patients with baseline BEC ≥ 300 cells/µL, a pooled analysis which stratified patients by baseline BEC (≥ 0 cells/µL, ≥ 150 cells/µL, ≥ 300 cells/µL, and ≥ 450 cells/µL) found Fasenra to have a statistically significant positive treatment effect on those with baseline BEC ≥ 150 cells/µL. In addition, the ZONDA trial found Fasenra to significantly reduce oral corticosteroid dose in patients with baseline BEC ≥ 150 cells/µL. • The Global Initiative for Asthma (GINA) guidelines recommend Fasenra be considered as adjunct therapy for patients 12 years of age and older with exacerbations or poor symptom control despite taking at least high dose ICS/LABA and who have eosinophilic biomarkers or need maintenance oral corticosteroids.
    • Patients could potentially meet asthma criteria for both Xolair and Fasenra, though there is insufficient data to support the combination use of multiple asthma biologics. The combination has not been studied. Approximately 30% of patients in the Nucala MENSA study also were candidates for therapy with Xolair. • Lab results for blood eosinophil counts can be converted into cells/mcL using the following unit conversion calculator: https://www.fasenrahcp.com/m/fasenra-eosinophil- calculator.html.
    • PDC is a measure of adherence. PDC is calculated as the sum of days covered in a time frame divided by the number of days in the time frame. To achieve a PDC of 0.8, a member must have received their asthma controller therapy for 144 days out of the last 180 days, or approximately 5 months of the last 6 months. Page 5 of 8

    CLINICAL POLICY Benralizumab V. Dosage and Administration
    Indication Severe asthma Dosing Regimen 30 mg SC every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter Maximum Dose See regimen VI. Product Availability
    • Single-dose prefilled syringe with solution for injection: 30 mg/mL
    • Single-dose autoinjector Fasenra Pen with solution for injection: 30 mg/mL VII.