Sunflower Health Plan NUCALA, Mepolizumab Form

Mepolizumab (Nucala®) is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa). FDA Approved Indication(s) Nucala is indicated for: • Add-on maintenance treatment of patients with severe asthma aged 6 years and older, and with an eosinophilic phenotype. • 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. • Treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). • 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. Limitation(s) of use: Nucala 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 Nucala 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; 3. Prescribed by or in consultation with a pulmonologist, immunologist, or allergist; 4. Age ≥ 6 years; 5. Member has experienced ≥ 2 exacerbations with in 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 beta-2 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; Page 1 of 14 CLINICAL POLICY Mepolizumab c. Intubation; 6. Nucala is prescribed concurrently with an ICS plus either a LABA or LTRA; 7. Nucala is not prescribed concurrently with Cinqair®, Fasenra®, Dupixent®, Xolair®, or Tezspire®; 8. Dose does not exceed (a or b): a. Age 6 to 11 years: 40 mg every 4 weeks; b. Age ≥ 12 years: 100 mg every 4 weeks. Approval duration: 6 months B. Eosinophilic Granulomatosis with Polyangiitis (formerly Churg-Strauss) (must meet all): 1. Diagnosis of EGPA (formerly Churg-Strauss) defined as presence of all of the following (a, b, and c): a. Asthma; b. At least 2 of the following characteristics of EGPA (i-ix): i. Histopathological evidence of eosinophilic vasculitis, perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation; ii. Neuropathy; iii. Pulmonary infiltrates; iv. Sino-nasal abnormality; v. Cardiomyopathy; vi. Glomerulonephritis; vii. Alveolar hemorrhage; viii. Palpable purpura; ix. Antineutrophil cytoplasmic antibody (ANCA) positivity; c. Absolute blood eosinophil count ≥ 150 cells/mcL within the past 3 months; 2. Prescribed by or in consultation with a pulmonologist, rheumatologist, immunologist, or nephrologist; 3. Age ≥ 18 years; 4. One of the following (a or b): a. Member has experienced at least 1 relapse in the past 2 years while receiving a glucocorticoid, which required an increase in glucocorticoid dose, initiation or increase in other immunosuppressive therapy, or hospitalization; b. Member has refractory disease in the past 6 months, defined as either (i or ii): i. Failure to achieve remission following ≥ 3 month trial of a standard induction regimen (e.g., glucocorticoids, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil); ii. Recurrence of EGPA symptoms during glucocorticoid dose taper; 5. Failure of a 4-week trial of a glucocorticoid (see Appendix B), unless contraindicated or clinically significant adverse events are experienced; 6. Nucala is not prescribed concurrently with Cinqair, Fasenra, Dupixent, Xolair, or Tezspire; 7. Dose does not exceed 300 mg every 4 weeks. Approval duration: 6 months Page 2 of 14 CLINICAL POLICY Mepolizumab C. Hypereosinophilic Syndrome (must meet all): 1. Diagnosis of HES with all of the following characteristics (a, b, and c): a. FIP1L1-PDGFRα negative; b. Does not have a non-hematologic secondary cause (e.g., drug sensitivity, parasite helminth infection, HIV infection, non-hematological malignancy); c. Uncontrolled, defined as a history of ≥ 2 flares (see Appendix D) within the past 12 months; 2. Prescribed by or in consultation with a hematologist, dermatologist, or immunologist; 3. Age ≥ 12 years; 4. Member has a blood eosinophil count ≥ 1,000 cells/mcL within the past 3 months; 5. Failure of a 2-month trial of a corticosteroid (see Appendix B) within one of the following time frames (a or b), unless contraindicated or clinically significant adverse events are experienced: a. Within the last 6 months; b. Within the last year if the member’s current HES baseline therapy includes interferon-alfa, cyclosporine, azathioprine, hydroxyurea, or imatinib; 6. Nucala is prescribed concurrently with baseline HES therapy (e.g., oral corticosteroids, immunosuppressive therapy); 7. Nucala is not prescribed concurrently with Cinqair, Fasenra, Dupixent, Xolair, or Tezspire; 8. Dose does not exceed 300 mg every 4 weeks. Approval duration: 6 months D. Chronic Rhinosinusitis with Nasal Polyps (must meet all): 1. Diagnosis of CRSwNP with documentation of all of the following (a, b, and c): a. Presence of nasal polyps; b. Disease is bilateral; c. Member has experienced signs and symptoms (e.g., nasal congestion/blockage/ obstruction, loss of smell, rhinorrhea) for ≥ 12 weeks; 2. Prescribed by or in consultation with an allergist, immunologist, or otolaryngologist; 3. Age ≥ 18 years; 4. Member has required the use of systemic corticosteroids for symptom control within the last 2 years, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B for examples); 5. Failure of maintenance therapy with at least two intranasal corticosteroids, one of which must be Xhance™, each used for ≥ 4 weeks, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B for examples); 6. Nucala is prescribed concurrently with an intranasal corticosteroid, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B for examples); 7. Nucala is not prescribed concurrently with Cinqair, Dupixent, Fasenra, Xolair, or Tezspire; 8. Dose does not exceed 100 mg every 4 weeks. Approval duration: 6 months Page 3 of 14 CLINICAL POLICY Mepolizumab E. Other diagnoses/indications (must meet 1 or 2): 1. 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 2. 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): 1. 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); 2. Demonstrated adherence to asthma controller therapy (an ICS plus either an 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); 3. 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); 4. Nucala is not prescribed concurrently with Cinqair, Fasenra, Dupixent, Xolair, or Tezspire; 5. If request is for a dose increase, new dose does not exceed (a or b): a. Age 6 to 11 years: 40 mg every 4 weeks; b. Age ≥ 12 years: 100 mg every 4 weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or member’s renewal period, whichever is longer B. Eosinophilic Granulomatosis with Polyangiitis (formerly Churg-Strauss) (must meet all): 1. Member meets one of the following (a or b): Page 4 of 14 CLINICAL POLICY Mepolizumab 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); 2. Member is responding positively to therapy (examples may include but are not limited to: reduction of relapses or reduction in glucocorticoid dose); 3. Nucala is not prescribed concurrently with Cinqair, Fasenra, Dupixent, Xolair, or Tezspire; 4. If request is for a dose increase, new dose does not exceed 300 mg every 4 weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or member’s renewal period, whichever is longer C. Hypereosinophilic Syndrome (must meet all): 1. 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); 2. Member is responding positively to therapy with reduction in flares from baseline or reduction in maintenance HES therapy dose from baseline (see Appendix D); 3. Nucala is prescribed concurrently with baseline HES therapy (e.g., oral corticosteroids, immunosuppressive therapy); 4. Nucala is not prescribed concurrently with Cinqair, Fasenra, Dupixent, Xolair, or Tezspire; 5. If request is for a dose increase, new dose does not exceed 300 mg every 4 weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or member’s renewal period, whichever is longer D. Chronic Rhinosinusitis with Nasal Polyps (must meet all): 1. 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); 2. Demonstrated adherence to an intranasal corticosteroid, unless contraindicated or clinically significant adverse effects are experienced; 3. Member is responding positively to therapy (examples may include but are not limited to: reduced nasal polyp size, reduced need for systemic corticosteroids, improved sense of smell, improved quality of life); 4. Nucala is not prescribed concurrently with Cinqair, Dupixent, Fasenra, Xolair, or Tezspire; Page 5 of 14 CLINICAL POLICY Mepolizumab 5. If request is for a dose increase, new dose does not exceed 100 mg every 4 weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer E. Other diagnoses/indications (must meet 1 or 2): 1. 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 2. 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 CRSwNP: chronic rhinosinusitis with nasal polyps EGPA: eosinophilic granulomatosis with polyangiitis FDA: Food and Drug Administration FIP1L1-PDGFRα: Fip1-like1-platelet- derived growth factor receptor alpha GINA: Global Initiative for Asthma HES: hypereosinophilic syndrome ICS: inhaled corticosteroid LABA: long-acting beta-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. Page 6 of 14 CLINICAL POLICY Mepolizumab Drug Name Dosing Regimen Asthma - ICS (medium – high dose) Qvar (beclomethasone) budesonide (Pulmicort) Alvesco (ciclesonide) Flovent (fluticasone propionate) Arnuity Ellipta (fluticasone furoate) Asmanex (mometasone) Asthma - LABA Serevent (salmeterol) 50 mcg per dose 1 inhalation BID Asthma - Combination Products (ICS + LABA) Dulera (mometasone/ formoterol) Breo Ellipta (fluticasone/ vilanterol) Advair (fluticasone/ salmeterol) Fluticasone/salmeterol (Airduo RespiClick®) Symbicort (budesonide/ formoterol) Asthma - LTRA montelukast (Singulair) Dose Limit/ Maximum Dose 4 actuations BID 2 actuations BID 2 actuations BID 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 > 100 mcg/day 40 mcg, 80 mcg per actuation 1-4 actuations BID > 200 mcg/day 90 mcg, 180 mcg per actuation 2-4 actuations BID > 80 mcg/day 80 mcg, 160 mcg per actuation 1-2 actuations BID > 100 mcg/day 44-250 mcg per actuation 2-4 actuations BID ≥ 50 mcg/day 100 mcg, 200 mcg per actuation 1 actuation QD > 100 mcg/day HFA: 100 mcg, 200 mcg per actuation Twisthaler: 110 mcg, 220 mcg per actuation 1-2 actuations QD to BID 100/5 mcg, 200/5 mcg per actuation 2 actuations BID 100/25 mcg, 200/25 mcg per actuation 1 actuation QD 100/50 mcg, 250/50 mcg, 500/50 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 1-2 actuations BID 4 to 10 mg PO QD 10 mg per day Page 7 of 14 CLINICAL POLICY Mepolizumab Drug Name Dosing Regimen 10 to 20 mg PO BID 1,200 mg PO BID 1,200 mg PO BID Dose Limit/ Maximum Dose 40 mg per day 2,400 mg per day 2,400 mg per day 0.75 to 9 mg/day PO in 2 to 4 divided doses Varies 40 to 80 mg PO in 1 to 2 divided doses 40 to 80 mg PO in 1 to 2 divided doses 40 to 80 mg PO in 1 to 2 divided doses Varies Varies Varies zafirlukast (Accolate) zileuton ER (Zyflo CR) Zyflo (zileuton) Asthma - Oral Glucocorticoids dexamethasone (Decadron) methylprednisolone (Medrol) prednisolone (Millipred®, Orapred ODT®) prednisone (Deltasone®) EGPA methylprednisolone (Medrol) prednisone (Deltasone) cyclophosphamide* Varies Varies See regimen See regimen 25 mg/week 3 g/day Varies 20 million IU/m2/day 400 mg/day Varies Varies 80 mg/day 6.0 mg/day to 0.8 mg/kg/day 7.5 mg/day to 1 mg/kg/day 1-2 mg/kg/day PO or 0.5-1 g/m2/month IV 2-3 mg/kg PO QD 15 mg/week PO 1.5-3 g/day PO azathioprine* methotrexate* mycophenolate mofetil* HES oral corticosteroids:* prednisolone, prednisone interferon alfa-2b (Intron-A®) * 1 – 6.25 million IU 0.5 – 1 mg/kg/day subcutaneously daily 100 – 400 mg PO QD 150 – 500 mg PO QD 1 – 3 mg/kg PO QD 0.5 – 3 gm PO QD with or without corticosteroid imatinib (Gleevec®) cyclosporine* azathioprine* hydroxyurea* CRSwNP Intranasal corticosteroids beclomethasone (Beconase AQ, Qnasl) budesonide (Rhinocort Aqua, Rhinocort) flunisolide fluticasone propionate (Flonase) 1-2 sprays IN BID mometasone (Nasonex) 2 sprays IN BID 2 sprays IN BID Page 8 of 14 1-2 sprays IN BID 2 sprays/nostril BID 128 mcg IN QD or 200 mcg IN BID 1-2 inhalations/nostril/ day 2 sprays/nostril TID 2 sprays/nostril BID 2 sprays/nostril BID CLINICAL POLICY Mepolizumab Drug Name Dosing Regimen Omnaris, Zetonna (ciclesonide) Omnaris: 2 sprays IN QD Zetonna: 1 spray IN QD triamcinolone (Nasacort) Xhance™ (fluticasone propionate) 1 to 2 sprays (93 mcg/spray) to 2 sprays IN QD nostril IN BID Dose Limit/ Maximum Dose Omnaris: 2 sprays/ nostril/day Zetonna: 2 sprays/ nostril/day 2 sprays/ nostril/day 744 mcg/day Oral corticosteroids dexamethasone (Decadron) methylprednisolone (Medrol) prednisolone (Millipred, Orapred ODT) prednisone (Deltasone) 0.75 to 9 mg/day PO in 2 to 4 divided doses 4 to 48 mg PO in 1 to 2 divided doses 5 to 60 mg PO in 1 to 2 divided doses 5 to 60 mg PO in 1 to 2 divided doses Varies Varies Varies Varies 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. *Off-label Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity • Boxed warning(s): none reported Appendix D: General Information • Asthma: o The pivotal trials defined severe asthma as two or more exacerbations of asthma despite regular use of high-dose inhaled corticosteroids plus an additional controller with or without oral corticosteroids. Clinically significant exacerbation was defined as a worsening of asthma leading to the doubling (or more) of the existing maintenance dose of oral glucocorticoids for three or more days or hospital admission or an emergency department visit for asthma treatment. o The Global Initiative for Asthma (GINA) guidelines recommend Nucala be considered as adjunct therapy for patients 6 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. o Patients could potentially meet asthma criteria for both Xolair and Nucala, though data is insufficient to support combination use of multiple asthma biologics. The combination has not been studied. Approximately 30% of patients in the MENSA study also were candidates for therapy with Xolair. o 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 9 of 14 CLINICAL POLICY Mepolizumab • EGPA: o In the pivotal trial for treatment of EGPA, patients with a baseline blood eosinophil count < 150 cells/mcL did not have a statistically significant improvement in the primary endpoint, total accrued weeks of remission, when mepolizumab was compared to placebo (odds ratio, 0.95; 95% CI 0.28 to 3.24). Total number of weeks of remission was significantly greater in patients with a baseline eosinophil count ≥ 150 cells/mcL (odds ratio, 26.10; 95% CI 7.02 to 97.02). In addition, the pivotal study required patients to have relapsing or refractory, non-severe disease. o Standard of care for EGPA includes oral glucocorticoids. Induction therapy of prednisone 1 mg/kg/day is recommended for 2-3 weeks followed by gradual tapering to the minimal effective dose. Patients with stable doses of prednisone ≤ 7.5 mg/day are considered to be in remission, as defined by the European League Against Rheumatism (EULAR) and in the pivotal trial. The EGPA Consensus Task Force recommends that patients who are unable to taper prednisone to < 7.5 mg/day after 3- 4 months of therapy should be considered for additional immunosuppressant therapy. o EULAR defines an EGPA relapse as the appearance of new or worsening clinical manifestations, not including asthma and/or ear, nose, and throat. o Remission is defined as absence of clinical signs or symptoms attributed to EGPA on or off immunosuppressive therapy. Relapse is a recurrence of active disease following a period of remission. • Lab results for blood eosinophil counts can be converted into cells/mcL using the following unit conversion calculator: https://nucalahcp.com/severe-eosinophilic- asthma/eosinophils-and-moa/eosinophil-unit-calculator/ • Flares defined as a worsening of HES related clinical symptoms (e.g., pain, pruritus, skin lesions, nasal congestion, polyposis, dysphagia, or fatigue). An increase in blood eosinophil count requiring an escalation in therapy or above the predefined threshold level. An increase in maintenance oral corticosteroid dose by greater than or equal to 10 mg for 5 days or increase in/addition of any cytotoxic and/or immunosuppressive HES therapy. V. Dosage and Administration Dosing Regimen Indication Severe asthma Age 6 to 11 years: 40 mg SC every 4 weeks Age ≥ 12 years: 100 mg SC every 4 weeks 300 mg SC every 4 weeks 100 mg SC every 4 weeks EGPA, HES CRSwNP Maximum Dose 100 mg every 4 weeks 300 mg every 4 weeks 100 mg every 4 weeks VI. Product Availability • Single-dose vial: 100 mg of lyophilized powder for reconstitution • Single-dose prefilled glass syringe with needle for injection: 100 mg/mL • Single-dose prefilled autoinjector with needle for injection: 100 mg/mL • Single-dose prefilled glass syringe with needle for injection: 40 mg/0.4 mL Page 10 of 14 CLINICAL POLICY Mepolizumab VII.