BlueCross BlueShield of Tennessee Medical Policy Manual

Alpha1-Proteinase Inhibitor Therapy

NDC CODE(S)

00053-7201-XX Zemaira 1000 MG SOLR (CSL BEHRING)

 

00944-2814-XX Aralast NP 500 MG SOLR (BAXALTA)

 

00944-2815-XX Aralast NP 1000 MG SOLR (BAXALTA)

 

00944-2884-XX Glassia 1000 MG/50ML SOLN (BAXALTA)

 

13533-0700-XX Prolastin-C 1000 MG SOLR (GRIFOLS USA)

 

13533-0701-XX Prolastin-C 1000 MG SOLR (GRIFOLS USA)

 

13533-0703-XX Prolastin-C 1000 MG SOLR (GRIFOLS USA)

DESCRIPTION

The release of proteolytic enzymes such as trypsin and elastin through the blood onto organ surfaces and into tissue spaces results in tissue damage by a “digestive” process unless inhibitors are present. Alpha-1-antitrypsin (AAT), produced in the liver, is the most abundant of these serum protease inhibitors.  Also known as alpha1-proteinase inhibitor, it blocks the destructive action of trypsin and elastin as well as several other proteases.

While rare, the congenital condition of AAT deficiency is associated with the development of emphysema at an unusually early age and other conditions including increased incidence of neonatal hepatitis, usually progressing to cirrhosis. Normal reference values AAT 100-190 mg/dL with AAT Proteotype negative for S and Z phenotype (Non S Non Z) (Mayo Clinic). Some rare cases may have AAT levels of zero.  All individuals with AAT serum levels <70 mg/dL may have a homozygous deficiency and are at risk for early lung disease.

Alpha-1-antitrypsin prototyping should be done to confirm the presence of homozygous deficiency alleles.  Individuals who are severely deficient are typically homozygous in the Z allele with AAT levels 20 to 30% of normal.  Affected persons are extremely susceptible to cigarette smoking and may develop emphysema at an early age.  The form of emphysema is characteristically the panacinar type with predominant basal distribution.

Treatment of panacinar emphysema due to AAT deficiency with an alpha1-proteinase inhibitor is a process of chronic augmentation and maintenance therapy.  The products are prepared from pooled human plasma and purified to remove virus and DNA fragments.  The theoretical intent of augmentation is to protect the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors; however this has not been proven in any clinical trials.  Blood levels of circulating alpha1-proteinase inhibitor were found to increase after treatment. 

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA

INDICATION(S) DOSAGE & ADMINISTRATION
All indications 60 mg/kg by intravenous (IV) infusion administered once every 7 days (weekly)

LENGTH OF AUTHORIZATION

Coverage will be provided for 12 months and may be renewed.

Click here to view DOSAGE LIMITS

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

Reference values considered normal by the Mayo Clinic for alpha1-antitrypsin (AAT) levels are 100 to 190 mg/dL.  There are three major alleles in the AAT gene, The M is the full functioning, normal allele.  Therefore, the normal AAT prototype would be negative for S and Z phenotypes (non S and non Z, the abnormal alleles.)

No controlled studies were found in the published literature that validates the use of alpha-1-proteinase inhibitor for the treatment or prevention of other conditions or diseases.

SOURCES  

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2017, September). Alpha1-proteinase inhibitor human. Retrieved January 11, 2018 from MICROMEDEX Healthcare Series.

Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. 668-682. Accessed January 11, 2018.  doi: HTTP://DX.DOI.ORG/10.15326/JCOPDF.3.3.2015.0182

Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis. 2016; 3(3): 668-682

U. S. Food and Drug Administration. (2003, July). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Zemaira®. Retrieved January 11, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM172304.pdf.

U. S. Food and Drug Administration. (2010, April). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Prolastin®-C. Retrieved January 11, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM209676.pdf.

U. S. Food and Drug Administration. (2010, July). Center for Biologic Research and Evaluation. Glassia® (alpha1-proteinase inhibitor [human], intravenous). Retrieved January 11, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM217890.pdf.

Mayo Foundation for Medical Education and Research. (2016, June).Mayo Clinic. Test ID: A1ALC. Alpha-1-Antitrypsin Prototype S/Z by LC-MS/MS, Serum. Mayo medical laboratories. Retrieved May 9, 2016 from http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/61767.

Lexi-Comp Online. AHFS DI. (2017, March). α1-proteinase inhibitor (human). Retrieved January 11, 2018 from Lexi-Comp Online with AHFS.

U. S. Food and Drug Administration. (2017, September). Center for Biologic Research and Evaluation. Aralast® NP(alpha1-proteinase inhibitor [human]). Retrieved January11, 2018 fromhttp://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM051590.pdf.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:  3/13/2018

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information.

 

 

 

DOSAGE LIMITS

Maximum billable units per dose and over time by indication as a Medical Benefit: Billable Unit = 10 mg

Diagnosis

Dosage

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

700 billable units every 7 days