BlueCross BlueShield of Tennessee Medical Policy Manual

Alpha1-Proteinase Inhibitor Therapy

NDC CODE(S)

00944-2884-xx Glassia® 1g/50ml solution for injection Baxter 

 

00053-7201-xx Zemaira® 1g/20ml injection CSL Behring 

 

00944-2802-xx Aralast® NP 500 mg/25ml injection Baxter 

 

00944-2802-xx Aralast® NP 1 g/50ml injection  Baxter 

 

13533-0601-xx Prolastin® 500 mg/20ml injection  Talecris

 

13533-0601-xx Prolastin® 1 g/40 ml injection  Talecris 

 

13533-0700-xx Prolastin®-C 1g/20 ml injection  Grifols

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 (A1A), 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 A1A 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 A1A 100-190 mg/dL with A1A Proteotype negative for S and Z phenotype (Non S Non Z) (Mayo Clinic). Some rare cases may have A1A levels of zero.  All individuals with A1A serum levels <70 mg/dL may have a homozygous deficiency and are at risk for early lung disease.

Alpha-1-antitrypsin proteotyping should be done to confirm the presence of homozygous deficiency alleles.  Individuals who are severely deficient are typically homozygous in the Z allele with A1A 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 A1A 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.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA

INDICATION(S) DOSAGE & ADMINISTRATION
All indication 60 mg/kg by intravenous (IV) infusion weekly

 

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 

Reference values considered normal by the Mayo Clinic for alpha1-antitrypsin (A1A) levels are 100 to 190 mg/dL.  There are three major alleles in the A1A gene, The M is the full functioning, normal allele.  Therefore, the normal A1A proteotype would be negative for S and Z phenotypes (non S and non Z, the abnormal alleles.)

For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).

The safety and efficacy for the use of alpha1-proteinase inhibitor in the pediatric population has not been established.

There is insufficient evidence supporting the use of alpha1-proteinase inhibitor for the treatment of other conditions/diseases.

SOURCES

Lexi-Comp Online. AHFS DI. (2016, March). α1-proteinase inhibitor (human). Retrieved June 9, 2016 from Lexi-Comp Online with AHFS.

Mayo Foundation for Medical Education and Research. (2016, June).Mayo Clinic. Test ID: A1ALC. Alpha-1-Antitrypsin Proteotype 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.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, February). Alpha1-proteinase inhibitor human. Retrieved June 9, 2016 from MICROMEDEX Healthcare Series.

U. S. Food and Drug Administration. (2003, July). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Zemaira®. Retrieved June 9, 2016 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM172304.pdf.

U. S. Food and Drug Administration. (2009, April). Center for Biologic Research and Evaluation. Aralast® NP(alpha1-proteinase inhibitor [human]). Retrieved June 9, 2016 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM051590.pdf.

U. S. Food and Drug Administration. (2010, April). Center for Biologic Research and Evaluation. Alpha1-proteinase inhibitor (human) Prolastin®-C. Retrieved June 9, 2016 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 June 9, 2016 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM217890.pdf.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:  12/1/2016

ID_MRx

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.

Pharmaceutical Decision Support Tree

Alpha1-Proteinase Inhibitor Therapy (Aralast®-NP, Glassia®, Prolastin®-C, Zemaira®)

  1. Is this an initial request for the agent?

If yes, go to question #2

If no, go to question #7

  1. Is the requested medication being used to treat ANY ONE of the following?

If yes, this does not meet medical necessity and/or medical appropriateness criteria

If no, go to question #3

  1. Does the individual have a diagnosis of panacinar emphysema?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the individual 18 years of age or older with a confirmed diagnosis of congenital alpha1-antitrypsin (A1A) deficiency with ALL of the following?

If yes, go to question #5

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the number of billable units 700 or less (10 mg = 1 billable unit) every 7 days for a dosage of 60 mg/kg to be administered by intravenous (IV) infusion administered once every 7 days (weekly)?

If yes, go to question #6

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Will the maximum amount approved be for 6 months with renewal eligibility for maintenance therapy?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual continue to meet initial approval criteria from questions 2 through 6?

If yes, go to question #8

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual show disease response to therapy by ANY ONE of the following?

If yes, go to question #9

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Was there an absence of toxicity or immediate hypersensitivity reaction to the A1A product, such as anaphylaxis with the previous infusions?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.