Alpha 1-Antitrypsin Inhibitor Therapy

• Alpha 1-proteinase inhibitor (human) (Aralast NP™) intravenous infusion for administration a healthcare professional 
• Alpha 1-proteinase inhibitor (human) (Glassia®) intravenous infusion for administration by a healthcare professional 
• Alpha 1-proteinase inhibitor (human) (Prolastin®-C) intravenous infusion for administration by a healthcare professional
• Alpha 1-proteinase inhibitor (human) (Zemaira®) intravenous infusion for administration by a healthcare professional

• Alpha 1-Proteinase Inhibitor (Human) (Aralast NP™) 
  • For chronic augmentation therapy in adults with clinically evident emphysema due to severe congenital deficiency of alpha 1- proteinase inhibitor (A1-PI) (alpha 1-antitrypsin deficiency) 
  • Limitations of use: 
    • The effect of augmentation therapy with any A1-PI, including this product, on pulmonary exacerbations and on the progression of emphysema in alpha 1-antitrypsin deficiency has not been conclusively demonstrated in randomized, controlled clinical trials 
    • Clinical data demonstrating long-term effects of chronic augmentation and maintenance therapy of individuals with this product are not available 
    • This product is not indicated as therapy for lung disease in patients in whom severe A1-PI deficiency has not been established 
• Alpha 1-Proteinase Inhibitor (Human) (Glassia ®) 
  • For chronic augmentation and maintenance therapy in adults with clinically evident emphysema due to severe hereditary deficiency of alpha1-proteinase inhibitor (A1-PI) (alpha 1-antitrypsin deficiency) 
  • Limitations of use: 
    • The effect of augmentation therapy with any A1-PI, including this product, on pulmonary exacerbations and on the progression of emphysema in alpha 1-antitrypsin deficiency has not been conclusively demonstrated in randomized, controlled clinical trials 
    • Clinical data demonstrating long-term effects of chronic augmentation and maintenance therapy of individuals with this product are not available 
    • This product is not indicated as therapy for lung disease in patients in whom severe A1-PI deficiency has not been established
• Alpha 1-Proteinase Inhibitor (Human) (Prolastin®-C) 
  • For chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of alpha 1-proteinase inhibitor (A1-PI) (alpha 1-antitrypsin deficiency) 
  • Limitations of use: 
    • The effect of augmentation therapy with any A1-PI, including this product, on pulmonary exacerbations and on the progression of emphysema in A1-PI deficiency has not been conclusively demonstrated in randomized, controlled clinical trials 
    • Clinical data demonstrating long-term effects of chronic augmentation or maintenance therapy with this product are not available 
    • This product is not indicated as therapy for lung disease in patients in whom severe A1-PI deficiency has not been established 
• Alpha 1-Proteinase Inhibitor (Human) (Zemaira®) 
  • For chronic augmentation and maintenance therapy in adults with alpha 1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema 
  • Limitations of use:
    • The effect of augmentation therapy with this product or any A1-PI product on pulmonary exacerbations and on the progression of emphysema in A1-PI deficiency has not been demonstrated in randomized, controlled clinical studies
    • This product is not indicated as therapy for lung disease patients in whom severe A1-PI deficiency has not been established

The restricted product(s) may be considered medically necessary when the following criteria are met: 

1. The patient is 18 years of age or older; AND
2. The patient has a diagnosis of emphysema (medical record documentation required); AND
3. The patient is currently a non-smoker; AND 
4. The patient has a low pre-treatment serum concentration of alpha 1-antitrypsin (AAT) defined by ONE of the following (medical record documentation required):
   1. Less than 11 µmol/L (or less than 80 mg/dL) if measured by radial immunodiffusion; OR
   2. Less than 57 mg/dL if measured by nephelometry; AND
5. The patient has a diagnosis of congenital alpha 1-antitrypsin deficiency confirmed by presence of one of the following high-risk phenotypes (medical record documentation required):
   1. PiZZ, PiZ(null), or Pi(null)(null) protein phenotypes (homozygous); OR
   2. Other rare AAT disease-causing alleles associated with serum alpha1-antitrypsin (AAT) level less than 11µmol/L; AND
6. The patient is NOT immunoglobulin-A (IgA) antibody deficient with antibodies against IgA; AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies 

Duration of Approval: 365 days (1 year)

Other codes that may be applicable to this policy: S9346

1.  For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR
   4. Re-initiation of therapy, defined as ONE of the following:
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
   5. Requirement of a change in the requested restricted product formulation; AND
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.
   

All information referenced is from FDA package insert unless otherwise noted below. 

1. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1- antitrypsin. Am J Respir Crit Care Med. 1998 Jul;158(1):49-59.
2. Blanco I, Lara B, de Serres F. Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema. Orphanet Journal of Rare Diseases. 2011;6:14.
3. Griese M, et al. Alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients. European Respiratory Journal. 2007;29(2):240-50.
4. Griese M, Kappler M, Gaggar A, Hartl D. Inhibition of airway proteases in cystic fibrosis lung disease. European Respiratory Journal. 2008;32(3):783-95
5. Tonelli AR, Rouhani F, Li N, et al. Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank. Int J Chron Obstruct Pulmon Dis. 2009;4:443-52. 

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q4 annually.

September 2023: Criteria change: Adjusted diagnostic requirements for AAT serum concentration for clarity. Updated limitations of use for each product according to FDA label with no change to policy intent. Minor adjustments made to formatting and FDA labeled indications throughout policy for clarity according to FDA label with no change to policy intent. Updated maximum units per HCPCS code unit definitions.

June 2021: Criteria change: Added requirement of non-smoker to continuation section; added maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.

*Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy