Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Alpha 1-Antitrypsin Therapy (e.g., Prolastin-C®, Aralast NP™, Glassia™, Zemaira™)
Policy #:MA08.050

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, 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. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

MEDICALLY NECESSARY

Alpha 1-antitrypsin therapy (e.g., Prolastin-C®, Aralast NP, Glassia, Zemaira) is considered medically necessary and, therefore, covered for individuals who have alpha 1-antitrypsin 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 or less than 11 uM/L or less than 0.8 g/L (35 percent of normal), which is considered the threshold thought to protect against emphysema.
  • 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.

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.
Policy 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 (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 (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 (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 (Zemaira) was approved by the FDA on July 8, 2003, for treatment of individuals with deficiency and evidence of emphysema.

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. 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 PiZZ variant typically have a serum alpha 1-antitrypsin levels less than 35% of the average normal. Ninety-five percent of clinically symptomatic alpha 1-antitrypsin deficient individuals are PiZZ phenotype. Individuals with Pi(null)(null) are associated with undetectable serum alpha 1-antitrypsin levels or levels less than 1 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, PiSZ 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.

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

Alpha 1-Proteinase Inhibitor (Human) (Aralast NP). [Prescribing Information]. Westlake Village, CA: Baxter Healthcare Corporation. 2014. Updated 03/2014. Available at: http://www.baxter.com/downloads/healthcare_professionals/products/Aralast_NP_PI.pdf. Accessed September 22, 2016.

Alpha 1-Proteinase Inhibitor (Human) (Glassia). Prescribing Information]. Westlake Village, CA: Baxter Healthcare Corporation. 2014. Updated 03/2014. Available at: http://www.baxter.com/downloads/healthcare_professionals/products/Glassia_PI.pdf. Accessed September 22, 2016.

Alpha-1 Proteinase Inhibitor Human. Micromedex® Healthcare Series. DrugDex®. [Micromedex® Web site]. 05/30/14. Available at: http://www.thomsonhc.com/micromedex2/librarian [via subscription only]. Accessed September 22, 2016.

Alpha 1-Proteinase Inhibitor (Human) (Prolastin-C). [Prescribing Information]. Research Triangle Park, NC: Grifolis Therapeutics Inc. 2013. Updated 01/2013. Available at: http://www.grifols-pi.info/inserts/Prolastin-C.pdf. Accessed September 22, 2016.

Alpha 1-Proteinase Inhibitor (Human) (Zemaira). [Prescribing Information]. Kanakakee, IL: CSL Behring LLC. 2013. Updated 04/2013. Available at: http://labeling.cslbehring.com/PI/US/Zemaira/EN/Zemaira-Prescribing-Information.pdf. Accessed September 22, 2016.

American Hospital Formulary Service (AHFS). Drug Information 2014. Alpha 1-Proteinase Inhibitor (Human). [STAT!Ref Web site]. 07/08/2014. Available at: http://online.statref.com. [via subscription only]. Accessed September 22, 2016.

American Thoracic Society, et. al. 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;168:818-900.

Elsevier Gold Standard’s Clinical Pharmacology Compendium. Alpha-1-proteinase Inhibitor. [MD Consult Web site]. 07/19/2011. Available at: http://www.mdconsult.com/das/pharm/body/457431238-3/1537184989/full/1183. [via subscription only]. Accessed September 22, 2016.

Marciniuk, DD. et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: A Canadian Thoracic Society clinical practice guideline. Can Resp J. 2012;19(2):109-116.

Stockley, R. Alpha 1-antitrypsin review. Clin Chest Med. 2014;35:39-50.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Approval letter. Aralast NP. [FDA Web site]. 5/4/2007. Available at: http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm052477.htm. Accessed September 22, 2016.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Premarket approval letter. Glassia. [FDA Web site]. 7/1/10. Available at: http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm217888.htm Accessed September 22, 2016.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Approval letter. Zemaira. [FDA Web site]. 07/08/08. Available at: http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm055333.htm. Accessed September 22, 2016.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

E88.01 Alpha-1-antitrypsin deficiency

J43.1 Panlobular emphysema

J43.8 Other emphysema



HCPCS Level II Code Number(s)



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

J0257 Injection, alpha 1-proteinase inhibitor (human), (Glassia), 10MG

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


Revenue Code Number(s)

N/A

Coding and Billing Requirements






Policy History

MA08.050
09/26/2018This policy has been reissued in accordance with the Company's annual review process.
06/07/2017This policy has been reissued in accordance with the Company's annual review process.
11/09/2016This 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™).
10/14/2015This 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™).
01/01/2015This 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: 01/01/2015
Version Issued Date: 01/01/2015
Version Reissued Date: 09/27/2018