CurrentCignaPolicy IP0387

Alpha1-Proteinase Inhibitor Products

Cigna coverage policy for intravenous human alpha1-proteinase inhibitor products (Aralast NP, Glassia, Prolastin-C, Zemaira) used primarily for alpha1-antitrypsin deficiency with emphysema and for AAT deficiency–associated panniculitis; defines medical necessity criteria, prior authorization, dosing, and product-specific preferred product requirements for certain lines of business.

Policy Summary

PayerCigna

PolicyAlpha1-Proteinase Inhibitor Products

Policy CodePolicy IP0387

Change TypeAdded plan-specific preferred product requirements

Effective DateJun 1, 2025

Next Review Date

Key ActionSubmit prior authorization with required documentation (pretreatment AAT level, genotype/phenotype, baseline pulmonary function or biopsy for panniculitis, and prescriber specialty attestation) and, for Employer/Individual & Family plans after 2025-07-01, document trial and inability to take both Glassia and Prolastin‑C before requesting Aralast NP or Zemaira.

SourceLink

POLICY UPDATE CHANGES

Added Aralast NP and Zemaira preferred product requirements for Employer Plans and Individual and Family Plans, effective 2025-07-01.

Annual revision performed with no criteria changes as of 2025-03-15.

2FDA‑approved indications covered (emphysema/COPD with AAT deficiency; AAT‑associated panniculitis)

60 mg/kg weeklyStandard dosing for covered indications

J0256, J0257

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Medically Necessary and Not Covered Indications

Medically Necessary 6 Alpha1-Antitrypsin Deficiency with Emphysema (FDAad-approved)

Approve for 1 year if the patient meets ALL of the following (A, B, C, D, and E):

Medically Necessary 6 Alpha1-Antitrypsin DeficiencyadadAssociated Panniculitis (Supportive evidence)

Approve for 1 year if the patient meets ALL of the following (A, B, C, D, E, and F):

ALL of the following

Patient is ≥ 18 years of age
Diagnosis of panniculitis confirmed by skin biopsy
Documentation (biopsy report) required
Clinical severity and prior therapy
- Mild panniculitis
  - Patient experienced inadequate efficacy with dapsone
    Documentation required
  - Dapsone is contraindicated per prescriber
    Prescriber statement required
- Moderate to severe panniculitis
  - Patient has moderate to severe panniculitis
    Documentation required
Laboratory/genetic requirements
- Baseline alpha1-antitrypsin serum concentration < 11 mcmol/L
  Equivalent thresholds: < 80 mg/dL radial immunodiffusion; < 57 mg/dL nephelometry; documentation required
- Genotyping or phenotyping demonstrates one of: ZZ, (null)(null), Z(null), SZ, or other rare disease-causing alleles associated with serum AAT < 11 mcmol/L
  Documentation required
Medication is prescribed by, or in consultation with, a dermatologist or pulmonologist
Preferred product criteria is met for the product(s) as listed in plan‑specific tables

Not Medically Necessary / Not Covered

Alpha1-proteinase inhibitor products are considered not medically necessary for any indication not listed as medically necessary below, including but not limited to:

ANY of the following

Alpha1-Antitrypsin deficiency without lung disease (even if AAT deficiency–related hepatic disease is present)
Bronchiectasis without alpha1-antitrypsin deficiency
Chronic Obstructive Pulmonary Disease (COPD) without alpha1-antitrypsin deficiency
Any other non‑listed or investigational indications (policy may be updated as new data are available)

Billing Codes

Covered HCPCS codes (when criteria met)HCPCSCovered

J0256	Injection, alpha 1-proteinase inhibitor (human), not otherwise specified, 10 mg
J0257	Injection, alpha 1 proteinase inhibitor (human), (Glassia), 10 mg
J7699	NOC drugs, inhalation solution administered through DME

Authorization, Documentation, and Plan Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for medical benefit coverage of alpha1-proteinase inhibitor products; approvals are provided when the criteria and dosing in the policy are met and are typically for 1 year. Covered HCPCS codes when criteria are met include: J0256, J0257, and J7699.

J0256
J0257
J7699

Documentation Required

Required documentation

Providers must supply the documentation specified in the criteria prior to approval, including pretreatment AAT serum concentration, genotype/phenotype results, baseline pulmonary function or oxygen requirement, biopsy for panniculitis where applicable, and prescriber specialty consultation/attestation.

Pretreatment alpha1-antitrypsin serum concentration (e.g., < 11 mcmol/L or corresponding mg/dL thresholds)

Clinical Thresholds and Standard Dosing

Key Thresholds and Dosing

AAT serum concentration (nephelometry)< 57 mg/dL (nephelometry threshold associated with AAT deficiency with lung disease)

AAT serum concentration (radial immunodiffusion)< 80 mg/dL (older radial immunodiffusion equivalence corresponding to 11 mcmol/L)

Protective threshold11 mcmol/L (theoretical protective threshold / target to raise serum AAT above)

FEV1 baseline cutoff< 65% predicted (one baseline respiratory criterion for augmentation therapy)

Accelerated FEV1 decline> 100 mL/year (counts as accelerated decline criterion)

DLCO decline> 15% per year (alternative accelerated decline criterion)

Clinical Background

Alpha1-antitrypsin (AAT) deficiency is an inherited, autosomal co‑dominant disorder characterized by abnormally low serum AAT concentrations that predispose to progressive emphysema, typically manifesting in adulthood. Diagnosis begins with quantitative measurement of plasma AAT; a serum AAT level below 11 mcmol/L (equivalent to 80 mg/dL by radial immunodiffusion or 57 mg/dL by nephelometry) identifies individuals at risk for AAT‑related lung disease. Low AAT levels permit unchecked protease activity in the lung, leading to destruction of alveolar tissue and airflow obstruction over time.

The goal of augmentation therapy with pooled human alpha1‑proteinase inhibitor is to raise serum AAT above a theoretical protective threshold of 11 mcmol/L, the level associated with lower probability of COPD in epidemiologic studies. Standard dosing for augmentation therapy (for emphysema and for AAT‑associated panniculitis) is 60 mg/kg intravenously once weekly. Evidence from professional society guidance and systematic reviews supports that intravenous augmentation slows progression of emphysema in patients with severe AAT deficiency, with the clearest benefit in nonsmokers and ex‑smokers who have airflow obstruction; augmentation therapy is not recommended for patients who continue to smoke.

AAT deficiency–associated panniculitis is an uncommon extrapulmonary manifestation that may respond to replacement of AAT. Although controlled trial evidence is limited, guideline reviews and case summaries indicate that augmentation with purified human alpha1‑proteinase inhibitor or plasma can be an effective treatment option when standard therapies (for example, dapsone) produce inadequate response or are contraindicated. For panniculitis when augmentation is used, the same 60 mg/kg weekly dosing is recommended in product labeling.

Defined Terms

Definitions

AATAlpha1-antitrypsin; a serum protease inhibitor deficient in alpha1-antitrypsin deficiency.

mcmol/L (mcM)Micromoles per liter; unit used for AAT protective threshold (11 mcmol/L).

Nephelometry vs radial immunodiffusionDifferent laboratory techniques for measuring AAT: nephelometry is the common current method (nephelometry threshold <57 mg/dL corresponds to disease), while older radial immunodiffusion overestimates levels so <80 mg/dL by that method corresponds to 11 mcmol/L.

Policy Changes

2025-07-01Material change — plan-specific preferred product requirementLatest

Effective 2025-07-01, for Employer Plans and Individual & Family Plans Aralast NP and Zemaira will require documentation that the patient has tried and cannot take BOTH Glassia and Prolastin‑C prior to coverage (material change).

2025-03-15Annual revision

Annual revision performed with no clinical criteria changes.

Quick Policy Metrics

2FDA‑approved indications covered

60 mg/kg weeklyStandard dosing for covered indications

J0256, J0257HCPCS product/drug codes listed

1 yearInitial approval duration for covered indications