ModifiedCentenePolicy CP PHAR.513

Plasminogen, Human-tvmh (Ryplazim) coverage

This policy governs coverage and prior authorization criteria for Ryplazim (plasminogen, human-tvmh) for treatment of plasminogen deficiency type 1 under Centene lines of business, affecting providers requesting therapy for covered members.

Policy Summary

PayerCentene

PolicyPlasminogen, Human-tvmh (Ryplazim) coverage

Policy CodePolicy CP PHAR.513

Change TypeCriteria, coding, and approval duration updates

Effective DateJun 4, 2021

Next Review DateN/A

Key ActionSubmit prior authorization with documentation (chart notes, labs) showing diagnosis, age (≥11 months), and required diagnostic criteria; include HCPCS J2998 on claims.

SourceLink

POLICY UPDATE CHANGES

Minimum age modified from at least 2 years to 11 months or older and diagnostic requirements changed from requiring all to two of three.

HCPCS code updated to include J2998 for injection, plasminogen, human-tvmh.

Commercial approval durations were revised to '6 months or to the member's renewal date, whichever is longer.'

6 monthsInitial approval duration

12 monthsContinued therapy duration (HIM/Medicaid)

<45%Lab threshold

J2998HCPCS code

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Coverage Criteria

Initial Therapy

Covered when ALL of the following are met for symptomatic congenital plasminogen deficiency (C-PLGD):

Initial criteria

Diagnostic evidence (need two): a) Presence of a PLG mutation; b) Signs or symptoms consistent with C-PLGD (see Appendix D); c) Plasminogen activity level < 45%.< 45% (for plasminogen activity)
Two of three diagnostic elements required
Prescriber: Medication is prescribed by or in consultation with a hematologist.
Dose limit: Requested dose does not exceed 6.6 mg/kg administered every second, third, or fourth day based on individual pharmacokinetics.6.6 mg/kg
Maximum dosing cap
Age requirement: Patient meets age requirement per prescribing information (see policy history for updates).
Minimum age requirements defined in policy history

Operational note: Provider must submit supporting documentation (office chart notes, lab results, or other clinical information) demonstrating the diagnostic elements, prescriber specialty, dosing calculations, and patient age.

Prior authorization required; include clinical documentation.

Continuation Therapy

Covered for continuation when ONE of the following is met:

Continued therapy criteria

Evidence of response: Member is responding positively to therapy as evidenced by improvement in C-PLGD signs or symptoms, reduction in size/number of visible lesions, imaging improvement of nonvisible lesions, or spirometry if pulmonary involvement.
Required to demonstrate continued benefit
Dose change: If request is for a dose increase, the new dose does not exceed 6.6 mg/kg every second, third, or fourth day.6.6 mg/kg
Maximum dosing cap for dose increases

Policy-level criteria notes

Policy history notes updates to clinical criteria per FDA labeling and internal reviews.

Age requirement: Patient is at least 11 months of age or older (updated from at least 2 years).>=11 months

Updated per prescribing information and policy history

Diagnostic requirements modified from requiring all three elements to documentation of any two of the three specified diagnostic elements (presence of PLG mutation; signs/symptoms consistent with C-PLGD; plasminogen activity < 45%).2 of 3

Refer to initial therapy diagnostic subcriteria for specifics

Approval duration: Commercial approvals are issued for 6 months or to the member's renewal date, whichever is longer; HIM/Medicaid approvals per policy (e.g., 12 months).6 months

Coverage for indications that are not included in the FDA-approved labeling is limited. Non‑FDA approved uses will only be considered when the requestor provides adequate documentation of efficacy and safety consistent with the referenced off‑label use policies (e.g., CP CPA.09 for commercial, HIM.PA.154 for marketplace, and CP PMN.53 for Medicaid) or per applicable evidence of coverage documents. Absent sufficient supporting documentation per those off‑label policies, requests for non‑labeled indications are not authorized.

When a member is covered under a state Medicaid program, any state Medicaid coverage provisions that conflict with this clinical policy take precedence. Providers should consult the applicable state Medicaid manual for the controlling coverage rules and follow those provisions over this policy where differences exist.

Uses of plasminogen for indications not addressed in the FDA label and not supported by the off‑label use policies cited are considered not authorized. Requests for non‑FDA approved indications must include the evidence required by the referenced off‑label policies; without that documentation, the use will be treated as not medically necessary and may be denied.

Policy history and updates reflect alignment with the FDA prescribing information and internal review. Approval criteria must be met as described in the policy, including any updated age and diagnostic requirements; failure to provide the required documentation (for example, evidence supporting the minimum age or the diagnostic elements) will result in denial of the request. Changes documented in the policy history (such as the minimum age revision to 11 months and modification of diagnostic criteria to two of three required elements) are enforceable requirements for authorization.

Coding

Policy Identifiermixed

CP PHAR.513

Policy reference number (internal)

Covered HCPCS CodesHCPCSCovered

J2998

Injection,plasminogen,human-tvmh; L mg

inv-10: Plasminogen activity level — laboratory threshold used in diagnostic criteria

Laboratory thresholdPlasminogen activity level < 45%

Use in diagnostic criteriaRequired as one of two of three diagnostic elements for C-PLGD (presence of PLG mutation; signs/symptoms consistent with C-PLGD; plasminogen activity <45%)

Threshold typeAbsolute activity percentage measured in laboratory assay

inv-11: Vial concentration — single-dose vial concentration after reconstitution

Concentration after reconstitution5.5 mg/mL

Vial volume50 mL per single-dose vial

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for initial and continuation therapy. Use HCPCS code J2998 (Injection, plasminogen, human-tvmh) when submitting prior authorization and claims.

Prior authorization required for initial and continuation approvals
Use HCPCS J2998 for PA and billing

Documentation Required

Required Documentation

Provider must submit supporting clinical documentation with the prior authorization request. Acceptable documentation includes office chart notes, relevant laboratory results (e.g., plasminogen activity level), diagnostic testing, imaging reports, and consultation notes that demonstrate the member meets the coverage criteria.

Include diagnosis and relevant clinical findings
Include patient age and any prior treatment history

Background

Congenital plasminogen deficiency (C‑PLGD; type 1, hypoplasminogenemia) is a rare autosomal‑recessive fibrinolytic disorder characterized by development of fibrin‑rich ligneous pseudomembranous lesions on mucous membranes and impaired wound healing. Clinical manifestations can include conjunctival, tracheobronchial, renal, oral, genitourinary, and central nervous system lesions, which may lead to significant morbidity if untreated.

This policy addresses use of plasminogen (Ryplazim) for symptomatic C‑PLGD and incorporates product availability and dosing considerations from the prescribing information. Relevant product details include single‑dose vials containing 68.8 mg (reconstituted concentration 5.5 mg/mL) and a dosing cap with a maximum of 6.6 mg/kg per dosing guidance. The policy was updated to align with FDA labeling and now requires diagnostic evidence meeting two of three specified elements and a minimum age of 11 months for authorization.

Definitions

inv-21: Definition of C-PLGD — diagnostic shorthand and brief definition

AbbreviationC-PLGD

DefinitionCongenital plasminogen deficiency (type 1 plasminogen deficiency or hypoplasminogenemia), a rare autosomal-recessive disorder causing ligneous pseudomembranous lesions and impaired fibrinolysis

Common clinical manifestationsLigneous conjunctivitis, tracheobronchial lesions, renal lesions, oral/genitourinary lesions, impaired wound healing

inv-22: Single-dose vial strength and concentration repeated in definitions for clarity

Single-dose vial strength and concentration68.8 mg in 50 mL vial (5.5 mg/mL after reconstitution)

Product referenceListed as single-dose vial product availability for plasminogen, human-tvmh