CurrentViva HealthPolicy IC-0052

Alpha-1-Proteinase Inhibitors: Aralast® NP; Glassia®; Prolastin®-C; Zemaira® (Intravenous)

Defines prior authorization, clinical eligibility, dosing, renewal, billing codes/NDCs, and allowable diagnoses for intravenous alpha-1-proteinase inhibitor products for emphysema due to AAT deficiency and steroid-refractory acute graft-versus-host disease (aGVHD). Applies to outpatient medical benefit administration.

Policy Summary

PayerViva Health

PolicyAlpha-1-Proteinase Inhibitors: Aralast® NP; Glassia®; Prolastin®-C; Zemaira® (Intravenous)

Policy CodePolicy IC-0052

Change TypeNo material change

Effective DateJan 1, 2012

Next Review Date

Key ActionPrior authorization is required; initial approvals valid for 12 months (365 days) except aGVHD (max 8 doses/4 weeks). Renewal may be granted every 12 months if renewal criteria met; aGVHD authorizations may not be renewed.

POLICY UPDATE CHANGES

No material change to coverage or clinical criteria

2Primary Covered Indications

12 monthsInitial Authorization Duration

2800Max billable units (AAT)

8Max doses for aGVHD

Coverage Summary

This policy covers intravenous alpha-1-proteinase inhibitor products — Aralast NP, Glassia, Prolastin‑C, and Zemaira — for outpatient medical benefit administration. Primary covered indications include treatment of emphysema due to alpha‑1‑antitrypsin (AAT) deficiency (FDA‑approved) and use for steroid‑refractory acute graft‑versus‑host disease (aGVHD) as recommended in compendia. Applicable FDA labeling and package inserts for each product and relevant clinical guidance (eg, NCCN Compendium and society guidelines) are referenced to define clinical eligibility, dosing, authorization duration, and renewal requirements.

Quick thresholds & limits

AAT serum concentration≤ 57 mg/dL (nephelometry) OR ≤ 11 µM/L (ELISA)

FEV1 percent predicted30–65% of predicted

Initial authorization duration12 months (365 days)

aGVHD maximum dosesUp to 8 doses over 4 weeks (authorization not renewable)

Max billable units per 28 days (AAT emphysema)2800 billable units per 28 days

Medical-Necessity Criteria

Initial Approval Criteria

Prior authorization validity is provided when ALL of the following are met:

ALL of the following

Universal Criteria
- Patient must have a contraindication, intolerance, or failure to Glassia ® AND Zemaira ® prior to the consideration of another alpha-1 proteinase inhibitor product
- Member is at least 18 years of age
- Member does NOT have any FDA labeled contraindications to the requested agent
Indication-specific: Emphysema due to alpha-1-antitrypsin (AAT) deficiency (FDA Approved; Prolastin-C orphan)
- FEV1 percent predicted: Member has an FEV1 in the range of 30-65% of predicted30-65% of predicted
- AAT serum concentration: Member has low serum concentration of AAT≤ 57 mg/dL (nephelometry) OR ≤ 11 µM/L (ELISA)
- Genotype: Member has alpha-1-antitrypsin (AAT) deficiency with PiZZ, PiZ (null), or Pi (null, null) phenotypes
- Imaging/clinical: Member has clinical evidence of panacinar/panlobular emphysema or centrilobular emphysema
- Smoking status: Member is not a tobacco smoker
- Concomitant therapy: Member is receiving optimal medical therapy (e.g., pharmacologic therapy such as bronchodilators, inhaled corticosteroids, comprehensive case management, pulmonary rehabilitation, vaccinations, smoking cessation, self-management skills, supplemental oxygen, etc.)
Indication-specific: Acute Graft Versus Host Disease (aGVHD) (Compendia Recommended)
- Transplant history: Member has received a hematopoietic stem cell transplant
- Indication: Used for steroid-refractory acute GVHD
- Therapy combination: Used in combination with systemic corticosteroids as additional therapy following no response to first-line therapy options

ref

title

Renewal Criteria

Prior authorization may be renewed when ALL of the following are met:

ALL of the following

Renewal general criteria: Member continues to meet the universal and other indication-specific relevant criteria identified in Initial Approval Criteria (section III), such as concomitant therapy requirements and performance status
Duration of authorization has not been exceeded (see Length of Authorization section)
Safety: Absence of unacceptable toxicity from the drug (examples include severe hypersensitivity reactions)
Emphysema-specific renewal evidence
- AAT response:

Authorization Duration and Limits

ALL of the following

Initial prior authorization validity: 12 months (365 days) unless otherwise specified12 months (365 days)
Renewal prior authorization validity: may be renewed every 12 months (365 days) thereafter unless otherwise specified12 months (365 days)
aGVHD duration and non-renewal: Acute GVHD: Prior authorization validity provided for a maximum of 8 doses (4 weeks); prior authorization for aGVHD may NOT be renewedMaximum of 8 doses (4 weeks)
aGVHD authorizations may not be renewed

Coding

Covered HCPCS codesHCPCSCovered

J0256	Aralast NP / Prolastin-C / Zemaira (1 billable unit = 10 mg)
J0257	Glassia (1 billable unit = 10 mg)

Covered NDCs (examples listed by product)NDCCovered

00944-2815-xx	Aralast NP, 1 g/50 mL
00944-2814-xx	Aralast NP, 0.5 g/25 mL
00944-2884-xx	Glassia, 1 g/50 mL
13533-0705-xx	Prolastin-C Liquid, multiple sizes (500 mg/10 mL; 1 g/20 mL; 4 g/80 mL)
00053-7201-xx	Zemaira, 1 g/20 mL
00053-7202-xx	Zemaira, 4 g/76 mL
00053-7203-xx	Zemaira, 5 g/95 mL

Covered ICD-10 diagnosis codesICD-10Covered

E88.01	Alpha-1-antitrypsin deficiency
D89.810	Acute graft-versus-host disease
D89.812	Acute on chronic graft-versus-host disease
D89.813	Graft-versus-host disease, unspecified
T86.09	Other complications of bone marrow transplant

Provider Actions & Billing

Prior Authorization

Prior authorization required

Prior authorization is required for alpha-1-proteinase inhibitor products. Initial approvals are valid for 12 months (365 days). For acute graft-versus-host disease (aGVHD), prior authorization is provided for a maximum of 8 doses (4 weeks) and may not be renewed. Renewals (when allowed) may be granted every 12 months if renewal criteria are met.

Documentation Required

Document prerequisite therapy and contraindications

Provider must document prior therapy and confirm key clinical eligibility elements before consideration of another alpha-1 product. Specifically, document a contraindication, intolerance, or treatment failure to both Glassia and Zemaira, and confirm the member meets phenotype, AAT level, FEV1 range, non-smoking status, and is receiving optimal medical therapy.

Evidence of contraindication/intolerance/failure to Glassia and Zemaira
AAT phenotype (PiZZ, PiZ null, or Pi null/null)
Serum AAT level ≤ 57 mg/dL (nephelometry) or ≤ 11 µM/L (ELISA)
Percent predicted FEV1 30–65%
Documentation member is not a current tobacco smoker
Evidence of optimal medical therapy (e.g., bronchodilators, inhaled corticosteroids, pulmonary rehab, vaccinations, smoking cessation, supplemental oxygen as applicable)

Billing Rule

Max units and dosing limits

Dosing and maximum billable unit limits differ by indication. For emphysema due to AAT deficiency, dosing is 60 mg/kg IV once weekly with a limit of 2800 billable units every 28 days. For aGVHD, dosing is 60 mg/kg IV given on days 1, 4, 8, 12, 16, 20, 24, and 28 (up to 8 doses) with up to 700 billable units per dose and a total of 5600 billable units over 28 days.

Affected HCPCS codes: J0256, J0257
Emphysema limit: 2800 units per 28 days (60 mg/kg weekly)
aGVHD limit: up to 700 units per dose; total 8 doses in 28 days = 5600 units per 28 days
aGVHD dose schedule: days 1, 4, 8, 12, 16, 20, 24, 28

Documentation Required

Renewal response documentation

For renewal in emphysema, providers must document treatment response and absence of unacceptable toxicity. Acceptable evidence of response includes elevation of AAT levels above baseline, a substantial reduction in the rate of decline in percent predicted FEV1, or improvement in CT scan lung density. Also document there is no unacceptable toxicity (for example, severe hypersensitivity).

Elevation of AAT level above baseline
Substantial reduction in rate of decline of percent predicted FEV1
Improvement in CT scan lung density
Documentation of absence of unacceptable toxicity (e.g., no severe hypersensitivity reactions)

Background & Evidence

Alpha‑1‑proteinase inhibitors are plasma‑derived AAT augmentation products (examples: Aralast NP, Glassia, Prolastin‑C, Zemaira) indicated for emphysema in patients with AAT deficiency and are also referenced in compendia/guidelines for use in steroid‑refractory aGVHD. The policy relies on FDA package labeling for individual products and on clinical sources including the NCCN Compendium and society statements/guidelines to specify clinical criteria (for example, FEV1 30–65% predicted, specific AAT phenotypes, and AAT serum concentration ≤ 57 mg/dL (nephelometry) or ≤ 11 µM/L (ELISA)), dosing (eg, 60 mg/kg IV regimens), and authorization limits. The document notes that orphan drug designation applies to Prolastin‑C as specified.

Evidence sources

Key clinical sourcesPackage inserts (Glassia 2025, Zemaira 2024, Aralast NP 2025, Prolastin-C 2020/2022); ATS/ERS 2003; ERS 2017; NCCN Compendia 2025/2026; select clinical studies and society guidelines as listed in references

Definitions

Billable unit1 billable unit = 10 mg for listed HCPCS codes

Orphan designationApplies only to Prolastin-C as noted

OpenPayer

Alpha-1-Proteinase Inhibitors: Aralast® NP; Glassia®; Prolastin®-C; Zemaira® (Intravenous)

Coverage Summary

Medical-Necessity Criteria

Coding

Provider Actions & Billing

Background & Evidence

Revision History