CurrentmhnPolicy CP.PHAR.94

Clinical Policy: Alpha1-Proteinase Inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira)

Defines prior authorization, medical necessity criteria, dosing limits, covered indications, exclusions, approval durations, and product availability for alpha1-proteinase inhibitor products (Aralast NP, Glassia, Prolastin-C, Zemaira) for Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Alpha1-Proteinase Inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira)

Policy CodePolicy CP.PHAR.94

Change TypeAnnual reviewno significant changes (1Q 2025)

Effective DateMar 1, 2012

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, etc.) supporting that member meets all approval criteria; alpha1-proteinase inhibitors require prior authorization.

SourceLink

POLICY UPDATE CHANGES

1Q 2025 annual review: no significant changes; references reviewed and updated.

1Q 2024 annual review: updated FDA approved indications section and added Aralast NP and Zemaira to HIM non-formulary disclaimer statements.

4Products covered

60 mg/kg/weekMaximum dose

Age ≥18Minimum age

6 monthsInitial approval duration

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Coverage Summary

Coverage stance: covered_with_criteria for Alpha1-Proteinase Inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira). Subject: Alpha1-Proteinase Inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira). Payer policy number: CP.PHAR.94. Effective date: 03.01.12; Last review: 02.25. Lines of business: Commercial, HIM, Medicaid. Summary: Aralast NP, Glassia, Prolastin-C, and Zemaira are covered when medical necessity criteria are met. Note: For Health Insurance Marketplace (HIM), pharmacy benefit requests for Aralast NP, Glassia, and Zemaira are non-formulary and should not be approved via these criteria; refer to HIM.PA.103 for the formulary exception process.

Thresholds and Key Criteria

Plasma AAT level< 11 micromol/L (≈50 mg/dL by nephelometry or 80 mg/dL by radial immunodiffusion)

FEV1 criteriaPost-bronchodilator FEV1 ≥30% to ≤65% predicted; OR FEV1 >65% to <80% predicted with rapid decline >100 mL/year

Cotinine test timingNegative nicotine metabolite (cotinine) test within the last 30 days

Maximum dosingDose does not exceed 60 mg/kg per week

Minimum ageAge ≥ 18 years

Initial approval durationTypical initial approval: 6 months (Commercial/Medicaid/HIM per policy details)

Initial Therapy Criteria — Alpha1-Antitrypsin Deficiency

I. Initial Approval Criteria - A. Alpha1-Antitrypsin Deficiency (must meet all)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of severe congenital AAT deficiency
Prescribed by or in consultation with a pulmonologist
Age ≥ 18 years
Member meets one of
- Documentation of plasma AAT level < 11 micromol/L (approximately 50 mg/dL using nephelometry or 80 mg/dL by radial immunodiffusion)< 11 micromol/L (approx. 50 mg/dL nephelometry or 80 mg/dL radial immunodiffusion)

Continuation (Renewal) Criteria

II. Continued Therapy - A. Alpha1-Antitrypsin Deficiency (must meet all)

Covered when ALL of the following are met:

ALL of the following

Member meets one of
- Currently receiving medication via Centene benefit or member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (refer to state addendums CC.PHARM.03A and CC.PHARM.03B)
  Refer to state-specific continuity addendums
Member is responding positively to therapy (improvement, maintenance, or stabilization in FEV1 rate of decline is acceptable evidence)
Improvement, maintenance, or stabilization acceptable

Unapproved Indications / Exclusions

III. Diagnoses/Indications NOT authorized

Not covered when any of the following apply:

ANY of the following

Non-FDA approved indications not addressed in this policy unless sufficient documentation of efficacy/safety per off-label policies or evidence of coverage documents
Refer to off-label/use and evidence of coverage policies
Immunoglobulin A (IgA) deficiency (IgA level less than 15 mg/dL) with known antibody against IgAIgA < 15 mg/dL with anti-IgA antibodies
Contraindication due to risk of severe hypersensitivity/anaphylaxis

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required

Provider must submit documentation (office notes, labs, or other clinical information) supporting that member meets all approval criteria. Alpha1-proteinase inhibitors require prior authorization. Relevant HCPCS J-codes: J0256 and J0257.

Submit office notes and laboratory results to support medical necessity

Documentation Required

AAT level and phenotype documentation

Provide plasma AAT level results and/or phenotype testing per criteria. Phenotypes that meet high-risk criteria include PiZZ, PiZnull, Pi(null, null), or selected rare phenotypes (e.g., Pi(Malton, Malton)). If plasma AAT level is < 11 micromol/L (≈50 mg/dL by nephelometry or ≈80 mg/dL by radial immunodiffusion) this meets the level criterion.

Applicable Codes

HCPCS J-codes referencedHCPCS

J0256	Injection, alpha 1 proteinase inhibitor (human), not otherwise specified, 10 mg
J0257	Injection, alpha 1 proteinase inhibitor (human), (Glassia), 10 mg

Clinical Evidence & Rationale

Evidence summary: Alpha1-proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira) are indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary/congenital AAT deficiency. The policy notes that the effect of augmentation therapy on pulmonary exacerbations and emphysema progression has not been conclusively demonstrated in randomized, controlled clinical trials, and long-term effects of chronic therapy are not available. FDA-approved indications and prescribing information for Aralast NP, Glassia, Prolastin-C, and Zemaira were reviewed (prescribing information 2020–2024).

Background

Background: Alpha1-proteinase inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira) are indicated as chronic augmentation and maintenance therapy for adults with clinical evidence of emphysema due to severe hereditary AAT deficiency. The policy specifies these products are not indicated for patients in whom severe alpha1-PI (AAT) deficiency has not been established.

Revision History

02.25annual reviewLatest

1Q 2025 annual review: no significant changes; references reviewed and updated; P&T Approval Date 02.25 (no clinical policy statement changes).

02.24annual review

1Q 2024 annual review: updated FDA approved indications section to align with prescriber information and added Aralast NP and Zemaira to HIM non-formulary disclaimer statements; references reviewed and updated; P&T Approval Date 02.24.

Policy Summary

Payermhn

PolicyClinical Policy: Alpha1-Proteinase Inhibitors (Aralast NP, Glassia, Prolastin-C, Zemaira)

Policy CodePolicy CP.PHAR.94

Change TypeAnnual reviewno significant changes (1Q 2025)

Effective DateMar 1, 2012

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, etc.) supporting that member meets all approval criteria; alpha1-proteinase inhibitors require prior authorization.

SourceLink

On This Page

If AAT level > 11 micromol/L, member has one of the high-risk phenotypes (e.g., PiZZ, PiZnull, Pi(null, null), or rare phenotypes such as Pi(Malton, Malton))AAT level > 11 micromol/L with listed high-risk phenotype

Member demonstrates clinical evidence of emphysema (one of)

FEV1 from ≥ 30% to ≤ 65% of predicted, post-bronchodilatorFEV1 ≥30% to ≤65% predicted (post-bronchodilator)
FEV1 from > 65% to < 80% of predicted, post-bronchodilator, AND a rapid decline in lung function showing a change in FEV1 > 100 mL per yearFEV1 >65% to <80% predicted (post-bronchodilator) AND decline >100 mL/year
Longitudinal data required to document decline

Member is not an active smoker as evidenced by recent (within the last 30 days) negative nicotine metabolite (i.e., cotinine) testNegative cotinine test within last 30 days

Dose does not exceed 60 mg/kg per week≤ 60 mg/kg per week

I. Initial Approval Criteria - B. Other diagnoses/indications (must meet 1 or 2)

If request does not fall under A, one of the following must be met:

ANY of the following

If the drug has undergone a label change within last 6 months not yet reflected in this policy, follow corresponding formulary/no coverage/non-formulary policies for the relevant line of business (references provided)Label change within last 6 months
Refer to listed policies per line of business
If requested use is not specifically listed under section III and criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business (references provided)Use not listed under section III and no recent label change
Refer to off-label use policies per line of business

If request is for a dose increase, new dose does not exceed 60 mg/kg per week≤ 60 mg/kg per week

Documentation Required

Pulmonary function documentation

Provide post-bronchodilator FEV1 percent predicted. If FEV1 is > 65% to < 80% predicted, include longitudinal data demonstrating a rapid decline in FEV1 > 100 mL per year.

Documentation Required

Smoking status verification

Provide evidence that the member is not an active smoker by submitting a negative nicotine metabolite (cotinine) test obtained within the last 30 days.

Billing Rule

Dose limit enforcement

Ensure the ordered dose does not exceed 60 mg/kg per week. Requests for dose increases must not exceed this maximum dosing limit.

Prior Authorization

Line-of-business HIM formulary exception

For the Health Insurance Marketplace (HIM) line of business, Aralast NP, Glassia, and Zemaira are non-formulary when requested via the pharmacy benefit and should not be approved using these criteria. Refer to HIM.PA.103 for formulary exception processes.