Background

Alpha–1 proteinase inhibitors (Aralast NP™, Glassia®, Prolastin-C®, or Zemaira™) are used for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha-1 proteinase inhibitor (A1-PI), also known as alpha1-antitrypsin deficiency (A1AD).

Policy (Criteria)

Aralast NP

Glassia

Prolastin–C

Zemaira

Coverage of these drugs is provided when the criteria below is met and for non-preferred products there has been a trial and failure of preferred therapy ((if applicable)).

Alpha–1 Proteinase Inhibitors may be considered MEDICALLY NECESSARY for the following condition(s) when all criteria is met:

1.  Diagnosis of congenital alpha-1 antitrypsin (AAT) deficiency
2. Diagnosis of emphysema
3. One of the following:
   • Pi*ZZ, Pi*Z(null) or Pi*(null)(null) protein phenotypes (homozygous)
   • Other rare AAT disease genotypes associated with pre-treatment serum alpha1-antitrypsin (AAT) level less than 11 micromole per liter [e.g., Pi(Malton, Malton), Pi(SZ)]
4. One of the following:
   • Circulating pre-treatment serum alpha1-antitrypsin (AAT) level less than 11 micromole per liter (which corresponds to less than 80 mg/dL if measured by radial immunodiffusion or less than 57 mg/dL if measured by nephelometry).
   • Member has a concomitant diagnosis of necrotizing panniculitis
5. Continued optimal conventional treatment for emphysema (e.g., bronchodilators)
6. One of the following:
   • The FEV1 level is less than or equal to 65 % of predicted
   • Member has experienced a rapid decline in lung function (i.e., reduction of FEV1 more than 120 mL/year) that warrants treatment
   • Member has a concomitant diagnosis of necrotizing panniculitis
7. Member is NOT a current smoker

Continuation of Alpha–1 Proteinase Inhibitors may be considered MEDICALLY NECESSARY for the following condition(s) when all criteria is met:

1. Demonstrate positive clinical response to therapy
2. Continued optimal conventional treatment for emphysema (e.g., bronchodilators)

Authorization duration: 12 months

References

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2021.
2. The American Thoracic Society. American Thoracic Society/European Respiratory Society Statement: Standards for the diagnosis and management of individuals with Alpha-1 antitrypsin deficiency.
3. Henao M, Craig T. Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook. Allergy And Asthma Proceedings.2017; 38(2):98-107.
4. Vogelmeier C, Criner G, Agustí A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. American Journal Of Respiratory And Critical Care Medicine. 2017; 195(5):557-582.
5. Polinski JM, Kowal MK, Gagnon M, et al. Home infusion: Safe clinically effective, patient preferred, and cost saving. Healthcare. 2016.
6. MCGTM Care Guidelines, 22nd edition, 2018, Home Infusion Therapy, CMT: CMT-0009(SR).
7. Micromedex DrugDex Compendium®. 2024. Alpha-1 Proteinase Inhibitors.
8. Clinical PharmacologyTM Compendium. 2024. Tampa FL: Gold Standard, Inc. Alpha-1 Proteinase Inhibitors.
9. Kueppers F, Andrake MD, Xu Q, Dunbrack RL, Kim J, Sanders CL. Protein modeling to assess the pathogenicity of rare variants of SERPINA1 in patients suspected of having Alpha 1 Antitrypsin Deficiency. BMC Med Genet. 2019. 20(1):125.
10. Wells AD, Woods A, Hilleman DE, Malesker MA. Alpha-1 antitrypsin replacement in patients with COPD. P&T: A Peer-Reviewed Journal for Managed Care & Formulary Management. 2019;44(7):412415.
11. Brantly ML, Lascano JE, Shahmohammadi A. Intravenous alpha-1 antitrypsin therapy for alpha-1 antitrypsin deficiency: the current state of the evidence. Chronic Obstr Pulm Dis. 2019;6(1):100-114.
12. Glassia (Alpha1-proteinase inhibitor (human)) [package insert]. Baxalta US Inc. Lexington, MA. Revised 09/2023.
13. Prolastin-C Liquid (Alpha1-proteinase inhibitor [human]) [package insert]. Grifols Therapeutics, LLC. Research Triangle Park, NC. Revised 05/2020.
14. Aralast (Alpha1-proteinase inhibitor (human)) [package insert]. Baxalta U.S. Inc., Lexington, MA. Revised 03/2023.
15. Zemaira (Alpha1-proteinase inhibitor (human)) [package insert]. CSL Behring, LLC. Kankakee, IL. Revised 09/2022.
16. [Alpha 1-Proteinase Inhibitor (Human)] In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated April 1, 2009.
17. Franciosi AN, Ralph J, O'Farrell NJ, et al. Alpha-1 antitrypsin deficiency-associated panniculitis. J Am Acad Dermatol. 2022;87(4):825-832.
18. Li Z, Franke RM, Morris DN, Yel L. Pharmacokinetics and Biochemical Efficacy of an α1 Proteinase Inhibitor (Aralast NP) in α1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis. Pulm Ther. 2022;8(3):311-326

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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