ARALAST NP, Alpha1-Proteinase Inhibitor (Human) GLASSIA, Alpha1-Proteinase Inhibitor (Human) ZEMAIRA, Alpha1-Proteinase Inhibitor (Human) PROLASTIN-C, Alpha1-Proteinase Inhibitor (Human) Form

The following are alpha1-proteinase inhibitors requiring prior authorization: alpha1-proteinase inhibitor, human (Aralast™ NP, Glassia®, Prolastin®-C, Zemaira®). ____ *For Health Insurance Marketplace (HIM), if request is through pharmacy benefit, Aralast NP, Glassia, and Zemaira are non-formulary and should not be approved using these criteria; refer to the formulary exception policy, HIM.PA.103. FDA Approved Indication(s) Aralast NP, Glassia, Prolastin-C, and Zemaira are indicated for chronic augmentation and maintenance therapy in adults (Aralast NP, Prolastin-C, Zemaira) or individuals (Glassia only)
• with clinical evidence of emphysema (Zemaira only) • with clinical evidence of emphysema due to severe congenital deficiency of alpha1-PI (alpha1-antitrypsin [AAT] deficiency) (Aralast NP) • with clinical evidence of emphysema due to severe hereditary deficiency of alpha1-PI (AAT deficiency) (Glassia and Prolastin-C) Aralast NP, Prolastin-C, and Zemaira increase antigenic and functional (anti-neutrophil elastase capacity) serum levels and antigenic lung epithelial lining fluid levels of alpha1-PI. Limitation(s) of use:
• The effect of augmentation therapy with alpha1-PI products on pulmonary exacerbations and on the progression of emphysema in alpha1-PI deficiency has not been conclusively demonstrated in randomized, controlled clinical trials.
• Clinical data demonstrating the long-term effects of chronic augmentation and maintenance therapy of individuals with alpha1-PI products are not available.
• Alpha1-PI products are not indicated as therapy for lung disease in patients in whom severe alpha1-PI deficiency has not been established. 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 Aralast NP, Glassia, Prolastin-C, and Zemaira are medically necessary when the following criteria are met:
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CLINICAL POLICY Alpha1-Proteinase Inhibitors I. Initial Approval Criteria
A. Alpha1-Antitrypsin Deficiency (must meet all):

1. Diagnosis of severe congenital AAT deficiency;
   
   2. Prescribed by or in consultation with a pulmonologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a or b): a. Documentation of plasma AAT level < 11 micromol/L (approximately 50 mg/dL using nephelometry or 80 mg/dL by radial immunodiffusion);
      b. If AAT level > 11 micromol/L, member has one of the high-risk phenotypes (i.e., PiZZ, PiZnull, Pi(null, null), or one of a few rare phenotypes [e.g., Pi(Malton, Malton)]);
2. Member demonstrates clinical evidence of emphysema (a or b):
   a. Forced expiratory volume in one second (FEV1) from ≥ 30% to ≤ 65% of predicted, post-bronchodilator;
   b. FEV1 from > 65% to < 80% of predicted, post-bronchodilator, and a rapid decline in lung function showing a change in FEV1 > 100 mL per year;
3. Member is not an active smoker as evidenced by recent (within the last 30 days) negative nicotine metabolite (i.e., cotinine) test;
4. Dose does not exceed 60 mg/kg per week.
   Approval duration:
   Medicaid – 6 months HIM – 6 months for Prolastin-C (refer to HIM.PA.103 for Aralast NP, Glassia, Zemaira) Commercial – 6 months or to the member’s renewal date, whichever is longer 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. Alpha1-Antitrypsin Deficiency (must meet all):

   1. Member meets one of the following (a or b): Page 2 of 7

   CLINICAL POLICY Alpha1-Proteinase Inhibitors 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;
   3. If request is for a dose increase, new dose does not exceed 60 mg/kg per week. Approval duration:
      Medicaid– 12 months HIM – 12 months for Prolastin-C (refer to HIM.PA.103 for Aralast NP, Glassia, Zemaira) Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):
7. 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

8. 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. Immunoglobulin A (IgA) deficiency (IgA level less than 15 mg/dL) with known antibody against IgA. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AAT: alpha1-antitrypsin alpha1-PI: alpha1-proteinase inhibitors COPD: chronic obstructive pulmonary disease FDA: Food and Drug Administration FEV1: forced expiratory volume in one second IgA: immunoglobulin A Page 3 of 7

   CLINICAL POLICY Alpha1-Proteinase Inhibitors Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s): use in IgA deficient patients with known antibodies against IgA and/or a history of anaphylaxis or other severe systemic reaction to alpha1-PI, due to the risk of severe hypersensitivity, including anaphylaxis. • Boxed warning(s): none reported Appendix D: General Information
   • The American Thoracic Society (ATS) and the European Respiratory Society (ERS) state that alpha1-proteinase inhibitor therapy does not confer benefit in, and is not recommended for, patients who have alpha1-proteinase-associated liver disease. • The 2016 COPD Foundation’s clinical practice guidelines for AAT deficiency in the adult recommend intravenous augmentation therapy for individuals with FEV1 less than 30% predicted with a weak recommendation with a low quality of evidence, and low value placed on the cost of this therapy. The 2003 ATS-ERS guidelines mirror the COPD Foundation in that evidence of benefit from augmentation therapy is weak in those with severe airflow obstruction.
   • Aralast NP, Glassia, Prolastin-C, Zemaira: Safety and effectiveness in the pediatric population have not been established • Smoking is an important risk factor for the development of emphysema in patients with AAT deficiency. Both the 2003 ATS and 2016 COPD Foundation AAT guidelines state that smoking cessation is important in this patient population. • The goal of AAT augmentation is to slow the progression of emphysema/lung function decline. Lung function can be measured with FEV1, which is most important predictor of survival of patients with emphysema due to AAT deficiency per the 2003 ATS AAT guidelines. Improvement, maintenance, or stabilization in FEV1 rate of decline is therefore an acceptable example of positive response to therapy. V. Dosage and Administration
   Indication Emphysema due to AAT deficiency Dosing Regimen 60 mg/kg IV once weekly Maximum Dose 60 mg/kg/week VI. Product Availability
   Drug Name Alpha1-proteinase inhibitor, human (Aralast NP) Alpha1-proteinase inhibitor, human (Glassia) Alpha1-proteinase inhibitor, human (Prolastin-C) Alpha1-proteinase inhibitor, human (Zemaira) Availability Single-use vial: 500 mg, 1,000 mg
   Single-use vial: 1,000 mg/50 mL Single-use vial: 1,000 mg (powder) Single-use vial: 500 mg/10 mL, 1,000 mg/20 mL, 4,000 mg/80 mL (liquid) Single-use vial: 1,000 mg, 4,000 mg, 5,000 mg Page 4 of 7

   CLINICAL POLICY Alpha1-Proteinase Inhibitors VII.