ModifiedHealth NetPolicy CP PHAR.513

Plasminogen (Ryplazim) coverage for congenital plasminogen deficiency

Defines medical necessity criteria, authorization duration, dosing limits, and documentation requirements for Ryplazim (plasminogen, human-tvmh) for members across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerHealth Net

PolicyPlasminogen (Ryplazim) coverage for congenital plasminogen deficiency

Policy CodePolicy CP PHAR.513

Change TypeMaterial revisions to age, diagnostic requirements, coding, and approval durations

Effective DateJun 4, 2021

Next Review Date

Key ActionRequest prior authorization and submit documentation showing diagnosis, required laboratory results, and that dosing does not exceed 6.6 mg/kg.

SourceLink

POLICY UPDATE CHANGES

Per prescribing information; modified minimum age from at least 2 years or older to 11 months or older and modified diagnostic requirements from all (a, b, and c) to two of three; removed requirement for increased trough plasminogen activity on continued therapy; HCPCS code updated.

Added HCPCS code J2998 for injection, plasminogen, human-tvmh.

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

J2998HCPCS added

11 monthsminimum age

6.6 mg/kgmax recommended dose

6 months

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

Initial Therapy — Covered when ALL of the following are met for initial therapy.

Covered when ALL of the following are met for initial therapy:

Initial Approval for C-PLGD: 1. Diagnosis of symptomatic congenital plasminogen deficiency (C-PLGD) as evidenced by documentation of two of the following (a–c): presence of a PLG mutation; signs or symptoms consistent with C-PLGD (see Appendix D); plasminogen activity level < 45%.Plasminogen activity < 45%

Document genetic testing, clinical signs (see Appendix D), and laboratory plasminogen activity.

Prescriber and Dosing Requirements: 2. Prescribed by or in consultation with a hematologist.

Dose must not exceed 6.6 mg/kg given every 2nd, 3rd, or 4th day based on individual pharmacokinetics.

Age Requirement: 3. Patient meets policy minimum age requirement.Minimum age: 11 months (per subsequent policy revision)

See policy history for the applied minimum age change.

Continuation Therapy — Continued therapy covered when ONE of the following is met.

Continued therapy covered when ONE of the following is met:

Continued Therapy - ongoing responder: a. Member is currently receiving the medication via the benefit or has previously met initial approval criteria AND is responding positively to therapy, evidenced by improvement in C-PLGD–associated signs or symptoms, reduction in size/number of visible lesions, improvement on imaging of nonvisible lesions, or improved spirometry if pulmonary involvement.

If request is for a dose increase, the new dose must not exceed 6.6 mg/kg every 2–4 days.

Continued Therapy - continuity of care: b. Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (refer to state-specific addendums).

Authorization durations differ by line of business (Commercial: 6 months or to member renewal date; HIM/Medicaid: 12 months).

Non‑FDA approved indications that are not specifically addressed in this policy are not covered unless the provider submits sufficient supporting documentation consistent with the payer's off‑label use requirements or applicable evidence‑of‑coverage documents. Refer to the plan's off‑label use policies (for example, CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP PMN.53 for Medicaid) when requesting coverage for an off‑label indication.

For members covered under Medicaid, state Medicaid coverage provisions supersede this clinical policy when there is a conflict. Providers must follow the applicable state Medicaid manual and billing guidance for any coverage determinations that differ from this policy.

Requests for therapy for non‑FDA approved indications that do not meet the plan's off‑label use documentation requirements are considered not authorized. Providers should include the clinical rationale, supporting literature, and any plan‑specified off‑label documentation when requesting prior authorization for such indications.

The inclusion or exclusion of billing codes in this clinical policy is for informational purposes only and does not guarantee coverage or payment. Claims may be denied if coding is inconsistent with current professional coding guidance; providers must use the most up‑to‑date coding references when submitting claims and follow plan submission requirements.

Coding, Dose & Product Details

Policy identifiersmixed

CP PHAR.513

Policy reference number (internal payer policy identifier)

HCPCS Codes referencedHCPCS

J2998

Injection, plasminogen, human-tvmh; L mg

Plasminogen activity and dosing — lab threshold and dosing frequency/maximum

Laboratory thresholdPlasminogen activity < 45%

Maximum recommended dose6.6 mg/kg per dose

Dosing frequencyEvery 2 to 4 days (every second, third, or fourth day based on individual pharmacokinetics)

Vial strength/concentration — single-dose vial strength after reconstitution and concentration

Single-dose vial strength (after reconstitution)68.8 mg per 50 mL vial

Concentration after reconstitution5.5 mg/mL of plasminogen

Prior Authorization, Documentation & Billing

Prior Authorization

Prior Authorization Required

Prior authorization is required for Ryplazim (plasminogen, human-tvmh). Prescriptions must be submitted by or in consultation with a hematologist when seeking initial approval. Prior authorization requests must use HCPCS code J2998 and include supporting clinical documentation to allow medical necessity review.

Prior authorization required for initial and continuation therapy
Prescribed by or in consultation with a hematologist for initial requests
Submit claims using HCPCS code J2998

Documentation Required

Documentation Required for Medical Necessity

Providers must submit office chart notes, relevant laboratory results (e.g., plasminogen activity levels), genetic testing showing a PLG mutation when available, and any other clinical information that documents diagnosis and treatment response. Requests lacking adequate clinical documentation (including for non‑FDA or off‑label uses) will be denied.

Clinical Background

Congenital plasminogen deficiency (type 1, C‑PLGD) is a rare autosomal‑recessive fibrinolytic disorder characterized by the formation of abnormal fibrin‑rich ("ligneous") lesions on mucous membranes and impaired wound healing. Ryplazim (plasminogen, human‑tvmh) is a human plasminogen replacement therapy approved for treatment of plasminogen deficiency and has shown improvements in plasminogen activity and C‑PLGD lesion manifestations in clinical studies.

Definitions

C-PLGD — definition of congenital plasminogen deficiency (type 1)

TermC-PLGD (congenital plasminogen deficiency, type 1)

CharacterizationA rare autosomal-recessive disorder of the fibrinolytic system characterized by abnormal extravascular accumulation and growth of fibrin-rich, woody (ligneous) pseudomembranous lesions on mucous membranes

Clinical impactLesions can occur in conjunctiva, respiratory tract, ears, oral cavity, cerebral ventricles, and genitourinary tract and may impair vision, breathing, hearing, or fertility

Ryplazim (plasminogen, human-tvmh) — product definition and prescribing information

Product nameRyplazim (plasminogen, human-tvmh)

DescriptionA human plasminogen replacement product FDA-approved for treatment of plasminogen deficiency (type 1); prescribing information referenced in policy