CurrentCignaPolicy IP0382

Ryplazim (plasminogen, human-tvmh) IV therapy

Defines prior authorization, coverage criteria, dosing, and documentation requirements for Ryplazim for treatment of congenital plasminogen deficiency type 1 for Cigna benefit plans.

Policy Summary

PayerCigna

PolicyRyplazim (plasminogen, human-tvmh) IV therapy

Policy CodePolicy IP0382

Change TypeAnnual revision — no material changes

Effective DateApr 15, 2026

Next Review Date

Key ActionObtain prior authorization; approvals are issued for initial 3 months and for 1 year for current users when criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3 monthsInitial approval duration

1 yearRenewal approval duration

6.6 mg/kgDose per administration

q2 daysMax dosing frequency

≤45%Baseline activity threshold

J2998HCPCS code

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

FDA-Approved Indication and Criteria

Approve for plasminogen deficiency type 1 when the following criteria are met:

Indication: Patient has plasminogen deficiency type 1 (hypoplasminogenemia)

FDA-approved indication

A: Initial Therapy (approve 3 months)

Genetic and lab confirmation: Patient has a diagnosis of plasminogen deficiency type 1 confirmed by BOTH: (a) biallelic pathogenic variants in the PLG gene; AND (b) baseline plasminogen activity level (prior to initiating Ryplazim) ≤ 45% of normal based on the reference range for the reporting laboratory≤ 45% of normal
Documentation required

Policy Summary

PayerCigna

PolicyRyplazim (plasminogen, human-tvmh) IV therapy

Policy CodePolicy IP0382

Change TypeAnnual revision — no material changes

Effective DateApr 15, 2026

Next Review Date

Key ActionObtain prior authorization; approvals are issued for initial 3 months and for 1 year for current users when criteria are met.

SourceLink

On This Page

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Coding and Dosing Key Points

Covered HCPCS CodesHCPCSCovered

J2998

Injection, plasminogen, human-tvmh, 1 mg

inv-05: Baseline plasminogen activity

Baseline plasminogen activity eligibility threshold≤ 45% of normal (based on the reference range for the reporting laboratory)

When measuredBaseline is measured prior to initiating Ryplazim therapy

DocumentationDocumentation of baseline plasminogen activity is required as part of initial therapy criteria

inv-06: Trough plasminogen activity change for response

Required trough plasminogen activity response threshold≥ 10% absolute increase above baseline trough level

When appliedUsed to demonstrate laboratory response for patients currently receiving Ryplazim (supports 1-year renewal)

Clinical decision guidanceIf trough ≥ 10% absolute increase above baseline, consider surgical removal of lesions in addition to plasminogen treatment

Provider Actions, Authorization & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for benefit coverage of Ryplazim. Approvals: initial therapy — authorize for 3 months when criteria are met; existing patients currently receiving Ryplazim — authorize for 1 year when continuation criteria are met. All approvals are provided for the duration noted (1 month = 30 days). Ryplazim must be prescribed by or in consultation with a physician who specializes in the condition being treated (hematologist). Requests for doses outside the dosing documented in the policy will be considered case-by-case by a clinician (Medical Director or Pharmacist).

Initial approvals: 3 months when ALL initial-therapy criteria are met
Continuation approvals (patient currently receiving Ryplazim): 1 year when continuation criteria are met
Approval duration interpretation: 1 month = 30 days
Dose exceptions: requests outside policy dosing reviewed case-by-case by clinician
Prescriber requirement: prescribed by or in consultation with a hematologist

Documentation Required

Documentation is required where noted in the criteria. Acceptable documentation includes chart notes, laboratory tests and results (including baseline and trough plasminogen activity levels), medical test results, claims records, prescription receipts, and other supporting information. All documentation must include patient-specific identifying information.

Documentation must be provided for genetic confirmation and baseline plasminogen activity (initial therapy)
Documentation examples: chart notes, labs, test results, claims records, prescription receipts
All documentation must include patient identifiers

Denial Risk

Coding / Claim Mismatches — Denial Risk

Claims submitted for services not accompanied by covered diagnosis or procedure codes under this Coverage Policy will be denied as not covered. When billing, providers must use the most appropriate codes as of the service date.

Claims lacking covered codes for the service will be denied
Providers must use the most appropriate diagnosis/procedure codes as of the submission date

Note

Provider Action Required

Provider action: ensure prior authorization is obtained before Ryplazim is furnished; provide required documentation (including genetic test results showing biallelic PLG pathogenic variants and baseline plasminogen activity level ≤ 45% for initial therapy, and evidence of clinical response or trough plasminogen activity improvement for continuation). Verify prescriber specialty (hematology) and that dosing matches policy dosing (6.6 mg/kg IV, not more frequently than once every other day).

Obtain prior authorization before dispensing/administering Ryplazim
For initial therapy, submit documentation of biallelic PLG pathogenic variants and baseline plasminogen activity ≤ 45% of normal
For continuation, submit documentation of clinical response or trough plasminogen activity ≥ 10% above baseline
Confirm Ryplazim prescribed by or in consultation with a hematologist
Use dosing: 6.6 mg/kg IV, not more frequently than once every other day

OpenPayer

Ryplazim (plasminogen, human-tvmh) IV therapy

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

Coding and Dosing Key Points

Provider Actions, Authorization & Documentation

Background

Definitions