ModifiedAnthemPolicy CC-0073

Alpha-1 Proteinase Inhibitor Therapy Clinical Criteria

Clinical criteria for medical-benefit coverage (prior authorization and continuation) of intravenous alpha-1 proteinase inhibitor products (Aralast NP, Glassia, Prolastin-C, Zemaira) for chronic augmentation therapy in adults with congenital alpha-1 antitrypsin deficiency and clinically evident emphysema.

Policy Summary

PayerAnthem

PolicyAlpha-1 Proteinase Inhibitor Therapy Clinical Criteria

Policy CodePolicy CC-0073

Change TypeRevised / Annual review updates (vial strengths, coding, criteria clarifications)

Effective DateDec 22, 2025

Next Review Date

Key ActionSubmit prior authorization with documentation of congenital AATD diagnosis, AAT serum level ≤11 µmol/L (or equivalent), clinically evident emphysema/COPD, non-smoker status, pre-initiation FEV1% predicted or evidence of rapid FEV1 decline (>120 mL/year), and IgA status/antibodies to IgA.

SourceLink

POLICY UPDATE CHANGES

Added new vial strengths for Glassia to quantity limit.

Moved criteria for antibodies to IgA into initial request section (2/21/2025).

Added continuation criteria (11/20/2020).

Added new vial strengths for Zemaira to quantity limit (11/15/2024).

4FDA-approved products listed

60 mg/kg weeklyDosing limit

≤11 µmol/LAAT threshold

Coverage Summary

Coverage stance: covered with criteria for intravenous alpha-1 proteinase inhibitor augmentation therapy in adults with congenital alpha-1 antitrypsin deficiency and clinically evident emphysema. Scope: medical-benefit prior authorization and continuation criteria for FDA-approved products Aralast NP, Glassia, Prolastin-C, and Zemaira. FDA-approved product count: 4. Dosing limits and billing guidance: dosing is limited to 60 mg/kg once weekly following product vial strengths. Eligibility thresholds referenced in criteria include an alpha-1 antitrypsin level of ≤ 11 µmol/L (≈ 80 mg/dL by radial immunodiffusion or 57 mg/dL by nephelometry), a pre-initiation FEV1 percent predicted range of 30–65% as one pathway to approval, and an alternative pathway of rapid lung function decline defined as an FEV1 decrease of > 120 mL/year.

Initial Therapy — Approval Criteria

Key clinical thresholds

Alpha-1 antitrypsin level≤ 11 µmol/L (≈ 80 mg/dL by radial immunodiffusion or 57 mg/dL by nephelometry)

FEV1 percent predicted30-65% prior to initiation

Rapid FEV1 decline> 120 mL/year

Dosage limit60 mg/kg once a week

Continuation Therapy — Approval Criteria

Documentation Required

Document response for continuation

Continuation of augmentation therapy requires documentation of clinically significant improvement or stabilization in signs and symptoms (for example, decreased frequency of exacerbations, slowed rate of FEV1 decline, preserved CT lung density, or improved symptom burden) and the individual must remain a non-smoker. Provide objective evidence supporting continued benefit when submitting a continuation request.

Decreased frequency of exacerbations
Slowed rate of FEV1 decline
Preservation of CT scan lung density
Improved symptom burden

Not Approved / Exclusions

Not approved / Exclusions

May not be approved when the above criteria are not met and for all other indications.

Denial Risk

Contraindication - IgA antibodies

Therapy is contraindicated and may be denied for individuals with antibodies to IgA because products contain trace amounts of IgA and such antibodies increase the risk of severe hypersensitivity or anaphylaxis. Note that alpha-1 proteinase inhibitor products are derived from pooled human plasma and may contain trace IgA.

Applicable Codes

HCPCS - Drug and infusion/service codes (informational)HCPCS

J0256	Injection, alpha 1-proteinase inhibitor (human), not otherwise specified, 10 mg [Aralast NP, Prolastin-C, Zemaira]
J0257	Injection, alpha 1 proteinase inhibitor (human), (Glassia), 10 mg
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

ICD-10 Diagnosis codes (informational)ICD-10

E88.01	Alpha-1-antitrypsin deficiency
J43.0-J43.9	Emphysema
J44.0-J44.9	Other chronic obstructive pulmonary disease

Provider Actions / Billing & Authorization

Prior Authorization

Prior authorization required

Prior authorization is required. Submit documentation of diagnosis of congenital alpha-1 antitrypsin deficiency, an AAT serum level ≤ 11 µmol/L (or equivalent testing conversion), evidence of clinically evident emphysema/COPD, current smoking status (individual must be a non-smoker), pre-initiation FEV1 percent predicted or evidence of rapid FEV1 decline (>120 mL/year), and IgA status/antibodies to IgA.

J0256
J0257
S9346

Billing Rule

Quantity limits / dosing

Dosing is limited to 60 mg/kg once weekly; follow product vial strengths when billing and apply the listed vial sizes for each product. When billing, use the appropriate HCPCS code per product and account for updated vial strengths in the quantity calculation.

Clinical Evidence & Guidelines

Evidence summary: Guideline recommendations include the American Thoracic Society/European Respiratory Society (ATS/ERS, 2003) statement recommending augmentation therapy for individuals with moderate airflow obstruction (FEV1 30–65% predicted) or a rapid decline in FEV1 of > 120 mL/year. Overall quality of the safety and efficacy evidence is described as poor or limited with unclear impact on clinical outcomes; this is reflected in the cited guideline and recent reviews listed in the references.

Evidence highlights

Guideline citationAmerican Thoracic Society/European Respiratory Society (ATS/ERS) 2003

Quality of evidenceSafety and efficacy data described as poor quality; unclear impact on outcomes; guidance still recommends for FEV1 30-65% or rapid decline

Background

Background: Augmentation therapy with plasma-derived alpha-1 proteinase inhibitors is intended to raise serum AAT above the protective threshold to slow progression of emphysema in congenital AATD. Products are derived from pooled human plasma and may contain trace amounts of IgA; individuals with antibodies to IgA (often associated with selective or severe IgA deficiency) are at increased risk for severe hypersensitivity and anaphylaxis, and therapy is contraindicated in those individuals. The ATS/ERS guidance is cited in the context of recommending therapy for those with moderate airflow obstruction or rapid FEV1 decline.

Clinically evident emphysema: Emphysema or COPD documented clinically or by imaging or physiology as specified in the approval criteria (i.e., findings consistent with clinically evident emphysema/COPD required for initiation).

Non-smoker: An individual who is currently not smoking; smoking status must be documented prior to initiation and for continuation of therapy.

Revision History

11/14/2025annual_reviewLatest

Annual review updated quantity limits and coding; Glassia vial strengths added and coding reviewed/expanded to include HCPCS S9346 and ICD-10 J44.0-J44.9; wording and formatting changes made; coding reviewed and updated in document history detail field for 11/14/2025 include addition of Glassia vial strengths and addition of HCPCS S9346 and ICD-10-CM J44.0-J44.9 in coding section of the policy document as noted in document history and quantity limits table for Glassia vial sizes (1000 mg, 4000 mg, 5000 mg).

02/21/2025select_review_clarification

Selection criteria clarified by moving criteria for antibodies to IgA into the initial request (approval) section of the clinical criteria; coding reviewed with no changes documented on this date.