CurrentBlue Cross Blue Shield - IowaPolicy 05.04.44

Ryplazim (plasminogen, human-tvmh) therapy for plasminogen deficiency type 1

Defines prior authorization, documentation, dosing limits, and coverage criteria for Ryplazim for members with plasminogen deficiency type 1 (hypoplasminogenemia) under Wellmark/Blue Cross Blue Shield - Iowa.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyRyplazim (plasminogen, human-tvmh) therapy for plasminogen deficiency type 1

Policy CodePolicy 05.04.44

Change TypeNo material changes

Effective DateJan 1, 2022

Next Review DateOct 1, 2025

Key ActionSubmit prior authorization with baseline plasminogen activity (≤ 45%) and documentation of lesions/symptoms for initial approval.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsauthorization period

≤ 45%baseline activity threshold

6.6 mg/kgclinical trial dosing

J2998HCPCS code

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

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inv-01: Initial Therapy (Plasminogen deficiency type 1)

Authorization of 12 months may be granted when ALL of the following are met:

Initial approval criteria: A. Member has a baseline plasminogen activity level of 45% or less.; B. Member has a documented history of lesions and symptoms consistent with a diagnosis of plasminogen deficiency type 1 (e.g., ligneous conjunctivitis, ligneous gingivitis or gingival overgrowth, vision abnormalities, respiratory distress and/or obstruction, abnormal wound healing).baseline plasminogen activity ≤ 45%

Authorization period: 12 months

inv-02: Continuation of Therapy

Authorization of 12 months may be granted for members with an approved indication who meet the following:

Continuation criteria: Member has an indication listed in the Criteria for Initial Approval and is experiencing benefit from therapy as evidenced by disease stability or improvement (e.g., improvement in lesion number and/or size, absence of new lesion development, improvement in respiratory function, increased quality of life).clinical evidence of stability or improvement

Authorization period: 12 months

This policy defines medical necessity and prior authorization requirements for Ryplazim (plasminogen, human-tvmh) under the member's contract. Benefit determinations are based on the applicable contract language in effect when services are rendered; exclusions, limitations, or exceptions may apply and individual member benefits must be verified with the payer.

This medical policy may not apply to Federal Employee Program (FEP) members. For FEP members, benefits and coverage rules are determined by the Federal Employee Program and Wellmark will not determine medical necessity when the FEP contract governs.

Initial Therapy — Specific Criteria

inv-14: Initial Therapy — Ryplazim

Initial authorization criteria for Ryplazim:

Initial therapy: Baseline plasminogen activity ≤ 45%; documented history of lesions and symptoms consistent with plasminogen deficiency type 1 (hypoplasminogenemia); authorization may be granted for 12 months.

Continuation Therapy — Renewal Criteria

inv-15: Continuation Therapy — Ryplazim

Continuation may be approved for 12 months when benefit is demonstrated.

Continuation: Member has an indication listed in Initial Therapy and demonstrates benefit from Ryplazim as evidenced by disease stability or improvement (e.g., reduction in lesion number/size, absence of new lesions, improved respiratory function, improved quality of life).

Authorization period: 12 months

Coding and Billing

Historical/Cancelled HCPCSHCPCS

C9090

Injection, plasminogen, human-tvmh, 1 mg (cancelled 7/1/2022)

Current HCPCSHCPCSCovered

J2998

Injection, plasminogen, human-tvmh, 1 mg (effective 7/1/2022)

inv-06: Baseline plasminogen activity

Baseline plasminogen activity threshold45% or less (≤ 45%)

Role in initial approvalRequired as part of initial authorization criteria for plasminogen deficiency type 1; must be documented in medical records

Evidence sourceUsed as enrollment criterion in pivotal study where participants had plasminogen activity ≤ 45%

Provider Actions, Documentation, and Denials

Prior Authorization

Prior Authorization Required

Prior authorization required. Initial approval may be granted for up to 12 months when criteria are met.

Authorization of 12 months may be granted when member meets clinical criteria for plasminogen deficiency type 1 (hypoplasminogenemia).

Billing Rule

Dosing Limits

Approvals may be subject to dosing limits consistent with FDA labeling, compendia, or guidelines.

Dosing and administration will follow FDA-approved labeling, accepted compendia, and evidence-based practice guidelines.

Documentation Required

Required Documentation

Submission of the following information is necessary to initiate the prior authorization review: Initial requests must include medical records (e.g., chart notes, lab reports) documenting a baseline plasminogen activity level and a history of lesions and symptoms consistent with diagnosis. Continuation requests must include medical records documenting disease stability or improvement.

Initial requests: baseline plasminogen activity level (documented as a lab report) and documented history of lesions/symptoms consistent with plasminogen deficiency type 1 (e.g., ligneous conjunctivitis, ligneous gingivitis/gingival overgrowth, vision abnormalities, respiratory distress/obstruction, abnormal wound healing).
Continuation requests: documentation of disease stability or improvement (chart notes, labs, imaging as applicable).

Denial Risk

Documentation-based Denials

Failure to provide the required initial or continuation documentation may result in denial of the request.

Denial risk includes missing baseline plasminogen activity level, lack of documented history of lesions/symptoms for initial requests, or absence of evidence of stability/improvement for continuation requests.

Background

Plasminogen deficiency type 1 (hypoplasminogenemia) is an ultra-rare, inherited disorder caused by mutations in the PLG gene leading to decreased plasminogen level and activity with resultant extravascular accumulation of fibrin-rich, ligneous lesions on mucous membranes.

Clinical manifestations commonly include ligneous conjunctivitis (the most frequent presentation, which can threaten vision), ligneous gingivitis or gingival overgrowth, respiratory tract obstruction or distress, impaired wound healing, and other site-specific fibrinous lesions. Ryplazim is a plasma‑derived human plasminogen replacement approved to temporarily restore plasminogen levels and reduce or resolve these lesions.

Definitions

inv-12: Plasminogen deficiency type 1

Definition (term)Plasminogen deficiency type 1 (hypoplasminogenemia)

PathophysiologyDecreased level and activity of plasminogen leading to extravascular accumulation of fibrin-rich, woody (ligneous) pseudomembranous lesions on mucous membranes

Common manifestationsLigneous conjunctivitis is the most common; may also involve oral cavity (ligneous gingivitis), respiratory tract, CNS (e.g., congenital occlusive hydrocephalus), ears, nasopharynx, GI and genitourinary tracts

inv-13: Plasminogen deficiency type 2

Definition (term)Plasminogen deficiency type 2 (dysplasminogenemia)

Key featureNormal plasminogen level but decreased plasminogen activity

Clinical impactOften asymptomatic

Site of Care and Infusion Considerations

Note

Infusion center administrations subject to dosing limits; no explicit site‑of‑care restriction

Approvals for infusion‑administered Ryplazim may be subject to the same dosing limits referenced in the policy (FDA labeling, compendia, guidelines); the policy does not impose an explicit site‑of‑care restriction but dosing limits still apply to infusion center administrations.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyRyplazim (plasminogen, human-tvmh) therapy for plasminogen deficiency type 1

Policy CodePolicy 05.04.44

Change TypeNo material changes

Effective DateJan 1, 2022

Next Review DateOct 1, 2025

Key ActionSubmit prior authorization with baseline plasminogen activity (≤ 45%) and documentation of lesions/symptoms for initial approval.

SourceLink

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