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 Update; Routine 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.

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

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
Dosing is in accordance with the United States Food and Drug Administration approved labeling

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.