Last Review Date: 04/04/2024

Date of Origin:  01/01/2012

Dates Reviewed:  12/2011, 02/2013, 08/2013, 06/2014, 06/2015, 01/2016, 10/2016, 03/2017, 09/2017, 12/2017, 03/2018, 06/2018, 04/2019, 04/2020, 04/2021, 04/2022, 04/2023, 04/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed, unless otherwise specified.

• Graft Versus Host Disease (GVHD): Coverage will be provided for a maximum of 8 doses (4 weeks) and may NOT be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Aralast NP 1 g/50 mL vial: 7 vials per week
• Aralast NP 0.5 g/25 mL vial: 1 vial per week
• Glassia 1 g/50 mL single use vial: 7 vials per week
• Prolastin-C 1 g/20 mL single-dose vial: 7 vials per week
• Prolastin-C Liquid 1g/20 mL single-dose vial: 7 vials per week
• Zemaira 1 g/20 mL single-use vial: 3 vials per week
• Zemaira 4 g/76 mL single-use vial: 1 vial per week
• Zemaira 5 g/95 mL single-use vial: 1 vial per week

B. Max Units (per dose and over time) [HCPCS Unit]:

   Emphysema due to alpha-1-antitrypsin (AAT) deficiency

• 700 billable units every 7 days

   GVHD

• 700 billable units for a total of 8 doses in 28 days

3. Initial Approval Criteria ^1-5

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1-5

• Patient does not have immunoglobulin-A (IgA) deficiency with antibodies against IgA; AND

Emphysema due to alpha-1-antitrypsin (AAT) deficiency † (Ф – orphan designation applies only to Prolastin-C) ^{1-6,8,9,12,16}

• Patient has an FEV₁ in the range of 30-65% of predicted; AND
• Patient has alpha-1-antitrypsin (AAT) deficiency with PiZZ, PiZ (null), or Pi (null, null) phenotypes; AND
• Patient has clinical evidence of panacinar/panlobular emphysema; AND
• Patient has low serum concentration of AAT ≤ 57 mg/dL (measured by nephelometry) or ≤ 11 µM/L (measured by ELISA); AND
• Patient is not a tobacco smoker; AND
• Patient is receiving optimal medical therapy (e.g., comprehensive case management, pulmonary rehabilitation, vaccinations, smoking cessation, self-management skills, etc.)

Graft Versus Host Disease (GVHD) ‡ ^13-15

• Patient has received a hematopoietic stem cell transplant; AND
• Used for steroid-refractory acute GVHD; AND
• Used in combination with systemic corticosteroids as additional therapy following no response to first-line therapy options

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-5

Coverage can be renewed based upon the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity reactions, etc.; AND

Emphysema due to alpha-1-antitrypsin (AAT) deficiency ^1-6,8,9

• Disease response with treatment as defined by elevation of AAT levels above baseline, substantial reduction in rate of deterioration of lung function as measured by percent predicted FEV₁, or improvement in CT scan lung density

Graft Versus Host Disease (GVHD) ^13-15

• Coverage may not be renewed

5. Dosage/Administration ^1-5,15

6. Billing Code/Availability Information

HCPCS Code(s) & NDC(s):

7. References

1. Glassia [package insert]. Lexington, MA; Takeda Pharmaceuticals USA, Inc.; September 2023. Accessed March 2024.
2. Zemaira [package insert]. Kankakee, IL; CSL Behring LLC; January 2024. Accessed March 2024.
3. Aralast NP [package insert]. Lexington, MA; Baxalta Inc.; March 2023. Accessed March 2024.
4. Prolastin-C Liquid [package insert]. Research Triangle Park, NC; Grifols Therapeutics, LLC; May 2020. Accessed March 2024.
5. Prolastin-C [package insert]. Research Triangle Park, NC; Grifols Therapeutics, LLC; January 2022. Accessed March 2024.
6. American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency. American Thoracic Society; European Respiratory Society. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
7. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2019.
8. Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis (Miami). 2016; 3(3):668-682.
9. Marciniuk DD, Hernandez P, Balter M, et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2012;19(2):109-16.
10. Stocks JM, Brantly M, Pollock D, et al. Multi-center study: the biochemical efficacy, safety and tolerability of a new α1-proteinase inhibitor, Zemaira. COPD. 2006;3:17–23.
11. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2023.
12. Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. Eur Respir J 2017; 50.
13. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Alpha1-Proteinase Inhibitor (Human). National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
14. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Hematopoietic Cell Transplantation (HCT). Version 3.2023. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
15. Magenau JM, Goldstein SC, Peltier D, et al. α1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018 Mar 22;131(12):1372-1379. doi: 10.1182/blood-2017-11-815746.
16. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2024 Report.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A