Medicare Advantage

Medical Policy

Notification

Alpha 1-Antitrypsin Therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira)

Notification Issue Date:

This version of the policy will become effective 03/02/2020.

The following criteria have been

added

to this policy:

The individual has a documented diagnosis of congenital alpha1-antitrypsin deficiency confirmed by one of the following:
- PiZZ, PiZ(null) or Pi(null)(null) protein phenotypes (homozygous)
- Other rare AAT disease-causing alleles associated with serum alpha1-antitrypsin (AAT) level <11µmol/L
The Individual must be 18 years or older for Alpha 1-antitrypsin therapy

The following

ICD-10 CM

code has been

deleted

from this policy:

J43.8 Other emphysema

The following HCPCS code has been deleted from this policy:

S9346 Home infusion therapy, alpha-1-proteinase inhibitor (e.g., Prolastin); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

The following ICD-10 CM code has been added to this policy:

J43.9 Emphysema, unspecified

________________________________

Note: on 01/14/2020 the following revisions were made to this policy in Notification:

ICD-10 code will NOT be added to this policy: J43.9 Emphysema, unspecified. This unspecified code will not be added and the more specific ICD-10 codes per policy criteria remain.

A billing requirement statement has been added to clarify, that for alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP™, Glassia™, Zemaira™), both of the following diagnoses are required:

E88.01 Alpha-1-antitrypsin deficiency AND J43.1 panlobular emphysema

Title:

Alpha 1-Antitrypsin Therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira)

Policy #:

MA08.050b

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

EMPHYSEMA WITH ALPHA 1-ANTITRYPSIN DEFICIENCY
Alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) is considered medically necessary and, therefore, covered for individuals 18 years of age and older who have alpha 1-antitrypsin (AAT) deficiency and clinical evidence of chronic emphysema without evidence of alpha 1-antitrypsin-associated liver disease, when all of the following criteria are met:

The individual has a low serum concentration of alpha 1-antitrypsin (AAT) less than 80 mg/dL (radial immunodiffusion) or 50 mg/dl (nephelometry) or less than 11 uM/L (nephelometry) or less than 0.8 g/L (35 percent of normal), which is considered the threshold thought to protect against emphysema.
The individual has a documented diagnosis of congenital alpha1-antitrypsin deficiency confirmed by one of the following:
- Pi*ZZ, Pi*Z(null) or Pi(null)(null) protein phenotypes (homozygous)
- Other rare AAT disease-causing alleles associated with serum alpha1-antitrypsin (AAT) level <11uM/L
The individual has progressive panacinar emphysema with a documented rate of decline in forced expiratory volume in 1 second (FEV1).
The individual is a non-smoker.

ACUTE GRAFT VERSUS HOST DISEASE (GVHD) AFTER HEMATOPOIETIC CELL TRANSPLANTATION
Alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) administered intravenously is considered medically necessary and, therefore, covered for individuals 18 years of age and older who have acute graft-versus-host disease (GVHD) following hematopoietic cell transplantation in conjunction with systemic corticosteroids following no response (steroid-refractory disease) to first-line therapy options.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

There is no Medicare coverage determination addressing this drug; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) is covered under a member's medical benefit (Part B benefit). It does not address instances when alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Alpha 1-proteinase inhibitor/Alpha 1-antitrypsin therapy (Prolastin-C) was approved by the FDA on October 16, 2009, for the treatment of individuals with alpha 1-antitrypsin deficiency and evidence of emphysema.

Alpha 1-proteinase inhibitor/Alpha 1-antitrypsin therapy (Aralast NP) was approved by the FDA on May 4, 2007, for chronic augmentation therapy in patients having alpha 1-antitrypsin deficiency with clinically evident emphysema.

Alpha 1-proteinase inhibitor/Alpha 1-antitrypsin therapy (Glassia) was approved by the FDA on July 1, 2010, and is indicated for chronic augmentation and maintenance therapy in adults with emphysema.

Alpha 1-proteinase inhibitor/Alpha 1-antitrypsin therapy (Zemaira) was approved by the FDA on July 8, 2003, for treatment of individuals with deficiency and evidence of emphysema.

PEDIATRIC USE

Alpha 1-antitrypsin therapy is not indicated for use in pediatric individuals less than 18 years of age.

Description

Alpha 1-antitrypsin (also known as congenital alpha 1-proteinase inhibitor) deficiency is an autosomal, codominant genetic disorder, differentiated by a deficient serum and lung concentrations of alpha 1-antitrypsin. The most common form of alpha1-antitrypsin deficiency is associated with allele Z, or homozygous proteinase inhibitor (Pi)*Z (ZZ). A deficiency in alpha 1-antitrypsin leaves the neutrophil elastase uninhibited. Uncontrolled neutrophil elastase leads to progressive destruction of the pulmonary connective tissue and loss of the alveoli.

Some individuals with certain phenotypic variants have an increased risk of developing progressive emphysema. Individuals with the Pi*ZZ variant typically have a serum alpha 1-antitrypsin levels less than 35 percent of the average normal. Ninety-five percent of clinically symptomatic alpha 1-antitrypsin deficient individuals are Pi*ZZ phenotype. Individuals with Pi(null)(null) are associated with undetectable serum alpha 1-antitrypsin levels or levels less than one percent of the normal amount. Individuals with these low serum alpha 1-antitrypsin levels have a markedly increased risk of developing emphysema over their lifetime. In addition, Pi*SZ individuals, whose serum alpha 1-antitrypsin levels range from approximately 9 to 23 uM, are considered to have moderately increased risk of developing emphysema.

Alpha-1 Antitrypsin (alpha proteinase inhibitor) is used as a replacement therapy for individuals with severe alpha 1-antitrypsin deficiency and clinical evidence of emphysema. Several biological drugs have been approved by the US Food and Drug Administration (FDA) for alpha 1-antitrypsin therapy, with orphan drug status. Prolastin, Aralast NP, Glassia, and Zemaira were approved by the FDA for the treatment of individuals with alpha 1-antitrypsin deficiency and evidence of emphysema. Prolastin was replaced by Prolastin-C in spring 2010.

Alpha 1-antitrypsin therapy (e.g., Prolastin-C, Aralast NP, Glassia, Zemaira) uses highly purified human alpha 1-antitrypsin derived from human plasma. Studies comparing alpha 1-antitrypsin preparations involved a limited number of participants with alpha 1-antitrypsin deficiency and emphysema. All preparations produced similar increases in the serum alpha 1-antitrypsin concentration and antigenic alpha 1-antitrypsin activity in lung epithelial lining fluid. Data from cohort studies, although limited, indicate that such replacement therapy is associated with a lower rate of decline of forced expiratory volume, thus protecting the lung tissue from further destruction. Safety and effectiveness have not been established in pediatric individuals.

American Thoracic Society guidelines recommend using Alpha 1-antitrypsin therapy for individuals with moderate airflow obstruction with a Forced Expiratory Volume in 1 second (FEV1) that is 30-65 percent predicted. The guidelines also recommend continuing optimal management of stable individuals with AAT deficiency which should include many of the interventions recommended for AAT-replete individuals with emphysema.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service (AHFS). Alpha 1-proteinase inhibitor (Human). Drug Information 2022. [Lexicomp Web site]. 03/28/2022. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 15, 2023.

American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.

Aralast^® NP (alpha-proteinase inhibitor [human]) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals, Inc. 12/22/2022. Available at: https://www.shirecontent.com/PI/PDFs/ARALASTNP_USA_ENG.pdf. Accessed March 15, 2023.

Elsevier's Clinical Pharmacology Compendium. Alpha-1-proteinase inhibitor. [Clinical Key Web site]. 03/08/2023. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed March 15, 2023.

Glassia^® (alpha-proteinase inhibitor [human]) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals, Inc. 09/27/2022. Available at: https://www.glassialiquid.com/. Accessed March 15, 2023.

IBM Micromedex^® DRUGDEX^® (electronic version). Alpha-1 proteinase inhibitor human. [Micromedex^® Web site]. IBM Watson Health, Greenwood Village, Colorado, USA. 03/10/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 15, 2023.

Lexi-Drugs Compendium. Alpha1-proteinase inhibitor. [Lexicomp Web site]. 01/30/2023. Available at: https://online.lexi.com/lso/action/home [via subscription only]. Accessed March 15, 2023.

Magenau JM, Goldstein SC, Peltier D, et al. Alpha 1-antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018;131(12):1372-1379.

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):109-116.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Hematopoietic Cell Transplantation (HCT). V3.2022. [NCCN Web site]. 01/24/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf. Accessed March 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. [NCCN Web site]. Alpha1-proteinase inhibitor (Human). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed March 15, 2023.

Prolastin^®-C (alpha-proteinase inhibitor [human]) [prescribing information]. Los Angeles, CA: Grifols USA, LLC. 09/21/2017. Available at: https://www.prolastin.com/en/hcp. Accessed March 15, 2023.

Stockley, RA. Alpha1-antitrypsin review. Clin Chest Med. 2014;35(1):39-50.

Stoller JK. Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency. [UpToDate Web site]. 09/13/2022. Available at: https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-natural-history-of-alpha-1-antitrypsin-deficiency?search=alpha 1 antitrypsin deficiency&source=search_result&selectedTitle=1~99&usage_type=default&display_rank=1 [via subscription only]. Accessed March 15, 2023.

Stoller JK. Treatment of alpha-1 antitrypsin deficiency. [UpToDate Web site]. 11/04/2021. Available at: https://www.uptodate.com/contents/treatment-of-alpha-1-antitrypsin-deficiency?search=Treatment of alpha-1 antitrypsin deficiency&source=search_result&selectedTitle=1~99&usage_type=default&display_rank=1 [via subscription only]. Accessed March 15, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Alpha 1-Proteinase Inhibitor (Human) (Aralast^® NP). Product Information. [FDA web site]. 12/22/2022. Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/aralast-np. Accessed March 15, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Alpha 1-Proteinase Inhibitor (Human) (Glassia^®). Prescribing Information. [FDA Web site]. 09/27/2022. Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/glassia. Accessed March 15, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Alpha 1-Proteinase Inhibitor (Human) (Prolastin^®-C). Prescribing Information. [FDA web site]. 09/21/2017. Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/prolastin-c. Accessed March 15, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Alpha 1-Proteinase Inhibitor (Human) (Zemaira^®). Prescribing Information. [FDA Web site]. 09/20/2022. Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/zemaira. Accessed March 15, 2023.

Zemaira^® (alpha proteinase [human]) [prescribing information]. Kankakee, IL: CSL Behring, LLC. Available at: https://www.zemaira.com/prescribing-information. Accessed March 15, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

EMPHYSEMA WITH ALPHA 1-ANTITRYPSIN DEFICIENCY

FOR Alpha 1-Antitrypsin THERAPY COVERAGE BOTH DIAGNOSES ARE REQUIRED

E88.01 Alpha-1-antitrypsin deficiency

AND THE FOLLOWING:

J43.1 Panlobular emphysema

ACUTE GRAFT VERSUS HOST DISEASE (GVHD) AFTER HEMATOPOIETIC CELL TRANSPLANTATION

FOR Alpha 1-Antitrypsin THERAPY COVERAGE BOTH DIAGNOSES ARE REQUIRED

ONE OF THE FOLLOWING:

D89.810 Acute graft-versus-host disease

D89.812 Acute on chronic graft-versus-host disease

D89.813 Graft-versus-host disease, unspecified

AND ONE OF THE FOLLOWING:

T86.09 Other complications of bone marrow transplant
Z94.81 Bone marrow transplant status

HCPCS Level II Code Number(s)

J0256 Injection, alpha 1 proteinase inhibitor (human), not otherwise specified, 10 mg

J0257 Injection, alpha 1 proteinase inhibitor (human), (GLASSIA), 10 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.050b:

04/05/2023	The policy has been reviewed and reissued to communicate the Company’s continuing position on alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP®, Glassia®, Zemaira®).
06/01/2022	The policy has been reviewed and reissued to communicate the Company’s continuing position on alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP®, Glassia®, Zemaira®).
11/17/2021	The policy has been reviewed and reissued to communicate the Company’s continuing position on alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP®, Glassia®, Zemaira®).
01/04/2021	This version of the policy will become effective 01/04/2021. The following criteria have been added to this policy in accordance with the National Comprehensive Cancer Network 03/23/2020: criteria for acute steroid-resistant graft versus host disease in individuals who have undergone a hematopoietic cell transplantation.

Revisions From MA08.050a:

03/02/2020

This version of the policy will become effective 03/02/2020.

The following criteria have been added to this policy:

The individual has a documented diagnosis of congenital alpha1-antitrypsin deficiency confirmed by one of the following:
- PiZZ, PiZ(null) or Pi(null)(null) protein phenotypes (homozygous)
- Other rare AAT disease-causing alleles associated with serum alpha1-antitrypsin (AAT) level <11µmol/L
The Individual must be 18 years or older for Alpha 1-antitrypsin therapy

The following ICD-10 CM code has been deleted from this policy:

J43.8 Other emphysema

The following HCPCS code has been deleted from this policy:

S9346 Home infusion therapy, alpha-1-proteinase inhibitor (e.g., Prolastin); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

The following ICD-10 CM code has been added to this policy:

J43.9 Emphysema, unspecified
________________________________

Note: on 01/14/2020 the following revisions were made to this policy in Notification:

ICD-10 code will NOT be added to this policy: J43.9 Emphysema, unspecified. This unspecified code will NOT be added and the more specific ICD-10 codes per policy criteria remain.

A billing requirement statement has been added to clarify, that for alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP™, Glassia™, Zemaira™), both of the following diagnoses are required:

E88.01 Alpha-1-antitrypsin deficiency AND J43.1 panlobular emphysema

Revisions From MA08.050:

09/26/2018	This policy has been reissued in accordance with the Company's annual review process.
06/07/2017	This policy has been reissued in accordance with the Company's annual review process.
11/09/2016	This policy has been reviewed and reissued to communicate the Company's continuing coverage of Alpha 1-antitrypsin therapy (eg, Prolastin-C®, Aralast NP™, Glassia™, Zemaira™).
10/14/2015	This policy has been reviewed and reissued to communicate the Company's continuing coverage of Alpha 1-antitrypsin therapy (eg, Prolastin-C®, Aralast NP™, Glassia™, Zemaira™).
01/01/2015	This is a new policy. This policy was posted for notification on 10/01/2014. On 10/02/2014, the policy was updated and contains the following modifications: The title of the policy was changed from Alpha 1-Proteinase Inhibitor Therapy (eg, Prolastin-C®, Aralast™, Aralast NP™, Glassia™, Zemaira™) to Alpha 1-Antitrypsin Therapy (eg, Prolastin-C®, Aralast NP™, Glassia™, Zemaira™). Aralast™ was removed from the policy as the drug is no longer available on the market.

Version Effective Date:

1/4/2021

Version Issued Date:

1/4/2021

Version Reissued Date:

4/5/2023