Currentsierra health and lifePolicy 2025D0070G

Ryplazim (Plasminogen, Human-Tvmh) Medical Benefit Drug Policy

Defines medical-benefit coverage criteria, continuation criteria, exclusions, applicable codes, and clinical rationale for Ryplazim (plasminogen, human-tvmh) for treatment of plasminogen deficiency type 1 (hypoplasminogenemia). Applies to UnitedHealthcare commercial/Community Plan and may inform Medicare Advantage determinations where applicable.

Policy Summary

Payersierra health and life

PolicyRyplazim (Plasminogen, Human-Tvmh) Medical Benefit Drug Policy

Policy CodePolicy 2025D0070G

Change TypeTemplate UpdateRoutine review (no content changes)

Effective DateMar 1, 2025

Next Review Date

Key ActionObtain prior authorization for initial Ryplazim therapy for up to 12 months and document plasminogen activity ≤ 45%, clinical signs/symptoms, hematologist involvement, and FDA-aligned dosing.

SourceLink

POLICY UPDATE CHANGES

07/01/2025 Template Update - Updated Benefit Considerations.

03/01/2025 Archived previous policy version 2024D0070F

1Covered Indication (FDA)

1Not covered indication (listed)

J2998Primary HCPCS code

Coverage Summary & Criteria

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UnitedHealthcare Commercial Medical Benefit Drug Policy: Ryplazim (Plasminogen, Human-Tvmh) — Policy Number 2025D0070G, Effective Date March 1, 2025. Coverage stance: Covered with criteria for Ryplazim (plasminogen, human-tvmh) for the treatment of plasminogen deficiency type 1 (hypoplasminogenemia), per the policy scope which applies to UnitedHealthcare commercial/Community Plan and may inform Medicare Advantage determinations where applicable.

Initial therapy (Medically necessary)

Ryplazim is proven and medically necessary for the treatment of plasminogen deficiency type 1 (hypoplasminogenemia) when ALL of the following are met:

Initial therapy (Medically necessary) - top level

Diagnosis of hypoplasminogenemia as measured by plasminogen activity level ≤ 45% of laboratory standardPlasminogen activity level ≤ 45% of laboratory standard
Clinical signs: Presence of clinical signs and symptoms of the disease (e.g., ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing, etc.)
Prescriber: Prescribed by or in consultation with a hematologist
Dosing is in accordance with the United States Food and Drug Administration approved labeling

Continuation therapy (Reauthorization)

Reauthorization is considered medically necessary when ALL of the following are met:

Continuation therapy (Reauthorization) - top level

Prior treatment: Patient has previously received treatment with Ryplazim therapy
Clinical response: Patient has experienced a positive clinical response to Ryplazim therapyPlasminogen trough increase ≥ 10 percentage points from baseline (response definition)
Examples include improved (reduction) in lesion number/size, improvement in wound-healing, plasminogen activity trough level has increased by at least 10 percentage points from baseline
Prescriber: Prescribed by or in consultation with a hematologist

Not medically necessary / Unproven

Ryplazim is unproven and not medically necessary for the following:

Not medically necessary / Unproven - top level

Idiopathic pulmonary fibrosis: Treatment of idiopathic pulmonary fibrosis

Prior Authorization & Documentation Requirements

Prior Authorization

Initial prior authorization requirements

Obtain prior authorization for initial Ryplazim therapy for up to 12 months. Document a plasminogen activity level ≤ 45% of laboratory standard, presence of clinical signs/symptoms of hypoplasminogenemia, that the drug is prescribed by or in consultation with a hematologist, and that dosing follows FDA-approved labeling.

J2998

Prior Authorization

Reauthorization / continuation documentation

For reauthorization (continuation) for up to 12 months, document prior treatment with Ryplazim and evidence of a positive clinical response (examples: reduction in lesion number/size, improved wound healing, or an increase in trough plasminogen activity of at least 10 percentage points from baseline). Also document that therapy is prescribed by or in consultation with a hematologist and that dosing continues to follow FDA-approved labeling.

J2998
Response threshold: ≥ 10 percentage point increase in trough plasminogen activity

Documentation Required

Diagnosis documentation

Document the diagnosis of plasminogen deficiency and supporting laboratory results, including measured plasma plasminogen activity.

ICD-10: E88.02

Evidence & Rationale

n=15RYPLAZIM trial 2 - n

78% external; 75% internalLesion resolution by wk 48

≥10% absolute increasePrimary endpoint: trough plasminogen activity

Evidence summary: Ryplazim received FDA approval as plasma-derived human plasminogen indicated for treatment of plasminogen deficiency type 1 (prescribing information Nov 2021). Clinical evidence from RYPLAZIM trial 2 (single-arm, open-label, n = 15) enrolled patients aged 4–42 years with baseline plasminogen activity between <5% and 45% of normal; dosing in the trial was 6.6 mg/kg every 2–4 days for 48 weeks. The trial’s primary endpoint was an absolute increase in trough plasminogen activity of at least a 10 percentage point increase from baseline, and by week 48 investigators reported resolution of 78% of external lesions and 75% of internal lesions. Clinical rationale: plasminogen replacement temporarily corrects plasminogen deficiency, increasing plasma plasminogen levels and reducing extravascular fibrin-rich (ligneous) lesions, which underlies the therapeutic benefit in hypoplasminogenemia.

Background & Definitions

Background: Plasminogen is a liver-synthesized protein converted to plasmin, which lyses fibrin clots and supports wound healing, angiogenesis, and tissue remodeling. Plasminogen deficiency type 1 (hypoplasminogenemia) is a rare autosomal-recessive disorder that causes abnormal extravascular accumulation of fibrin-rich ligneous pseudomembranous lesions on mucous membranes throughout the body; the most common manifestation is ligneous conjunctivitis, which can lead to visual impairment or blindness if untreated. Ryplazim, a plasma-derived human plasminogen product, is indicated to replace deficient plasminogen, temporarily correct the deficiency, and reduce fibrinous (ligneous) lesions. This policy defines medical-benefit coverage and continuation criteria, exclusions, applicable codes, and clinical rationale for Ryplazim and applies to UnitedHealthcare commercial/Community Plan.

Plasminogen activity level≤ 45% of laboratory standard

Plasminogen trough increase for responseabsolute increase of at least 10 percentage points from baseline

Term	Definition
Hypoplasminogenemia	Plasminogen deficiency type 1; low plasminogen activity leading to fibrin-rich ligneous lesions on mucous membranes.