CurrentUnitedHealthcarePolicy CSIND0070.07

Ryplazim (plasminogen, human-tvmh) — Indiana

Defines UnitedHealthcare Community Plan coverage criteria for Ryplazim (plasminogen, human-tvmh) for members in Indiana, including initial and continuation authorization requirements and excluded indications.

Policy Summary

PayerUnitedHealthcare

PolicyRyplazim (plasminogen, human-tvmh) — Indiana

Policy CodePolicy CSIND0070.07

Change TypeRoutine review — no material changes

Effective DateMar 1, 2025

Next Review Date

Key ActionObtain prior authorization and document baseline plasminogen activity ≤45% and clinical signs/symptoms; reauthorization requires evidence of clinical response (trough increase ≥10 percentage points).

SourceLink

POLICY UPDATE CHANGES

Routine review; no content changes.

≤45%diagnostic threshold

12 momax initial auth

12 momax reauth

J2998HCPCS

E88.02ICD-10

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 therapy criteria: Diagnosis of hypoplasminogenemia as measured by plasminogen activity level ≤ 45% of laboratory standard.plasminogen activity ≤ 45%

All conditions required

Clinical manifestations: Presence of clinical signs and symptoms of plasminogen deficiency (examples include ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing).

Prescriber requirement: Prescribed by or in consultation with a hematologist.

Policy Summary

PayerUnitedHealthcare

PolicyRyplazim (plasminogen, human-tvmh) — Indiana

Policy CodePolicy CSIND0070.07

Change TypeRoutine review — no material changes

Effective DateMar 1, 2025

Next Review Date

SourceLink

On This Page

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Continuation Therapy — Covered when ALL of the following are met for continuation of therapy

Covered when ALL of the following are met for continuation of therapy

Prior treatment: Patient has previously received treatment with Ryplazim therapy.

Clinical response: Patient has experienced a positive clinical response to Ryplazim (examples: reduction in lesion number or size, improvement in wound healing, or plasminogen activity trough level increased by at least 10 percentage points from baseline).trough increase ≥ 10 percentage points

Prescriber requirement: Prescribed by or in consultation with a hematologist.

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

Authorization duration: Reauthorization will be for no more than 12 months.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required for Ryplazim (plasminogen, human-tvmh) for treatment of plasminogen deficiency type 1 (hypoplasminogenemia). Initial and reauthorization approvals are time-limited (up to 12 months) and dosing must follow FDA‑approved labeling. Prescriber or consulting specialist must be a hematologist.

HCPCS: J2998 (Injection, plasminogen, human-tvmh, 1 mg)
Diagnosis: E88.02 (Plasminogen deficiency)

Step Therapy

No step therapy requirements specified for Ryplazim.

Documentation Required

Required Clinical Documentation

Document baseline plasminogen activity level and clinical signs/symptoms (e.g., ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing). Include documentation of prescriber specialty (hematologist) and dosing per FDA labeling. For continuation, document prior Ryplazim treatment and objective evidence of clinical response (e.g., reduction in lesion number/size, improved wound healing, or plasminogen activity trough increase ≥ 10 percentage points from baseline).

Baseline plasminogen activity level (≤ 45% for initial therapy)
Clinical signs/symptoms consistent with plasminogen deficiency type 1
Prescribing clinician is a hematologist or in consultation with one
Dosing schedule consistent with FDA labeling
For continuation: prior Ryplazim treatment and documented positive clinical response (e.g., ≥10 percentage point increase in trough plasminogen activity or ≥50% improvement in lesion number/size)

Denial Risk

Denial Triggers for Initial and Continuation Therapy

Denial risk if diagnostic, documentation, or prescriber criteria are not met. Examples include: plasminogen activity > 45% at baseline for initial therapy, absence of clinical signs/symptoms of plasminogen deficiency type 1, therapy not prescribed by or in consultation with a hematologist, dosing inconsistent with FDA labeling, or lack of documented positive clinical response for continuation.

Initial therapy denial triggers: baseline plasminogen activity > 45%; no documented clinical signs/symptoms; prescriber not a hematologist; dosing not per FDA labeling
Continuation therapy denial triggers: no prior Ryplazim therapy documented; no objective clinical improvement (e.g., <10 percentage point increase in trough plasminogen activity and no lesion improvement); prescriber not a hematologist; dosing not per FDA labeling

Background

Plasminogen is converted to plasmin, which mediates fibrin clot lysis and contributes to tissue remodeling. Plasminogen deficiency type 1 (hypoplasminogenemia) is a rare disorder marked by low plasminogen activity and accumulation of fibrin-rich lesions on mucous membranes; replacement with plasminogen can temporarily correct the deficiency and reduce such lesions.

Clinical management and coverage for Ryplazim are based on laboratory measurement of plasminogen activity and clinical signs: diagnosis requires plasminogen activity ≤ 45% of the laboratory standard, and response during a trial is defined as a trough plasminogen activity increase of ≥ 10 percentage points from baseline.

Definitions

Plasminogen deficiency type 1

DefinitionPlasminogen deficiency type 1 (hypoplasminogenemia): a rare autosomal-recessive disorder characterized by abnormally low plasminogen levels leading to accumulation of fibrin-rich ligneous pseudomembranous lesions on mucous membranes.

Common clinical manifestationLigneous conjunctivitis — inflamed, woody growths on conjunctival membranes that can lead to visual impairment or blindness if untreated.

PathophysiologyReduced plasminogen impairs conversion to plasmin, decreasing fibrin clot lysis and causing extravascular fibrin accumulation and lesion formation.

Therapeutic rationaleReplacement therapy with plasminogen can temporarily correct the deficiency and reduce fibrinous lesions by increasing plasma plasminogen levels.

Trial efficacy endpoint

Trial primary endpointIndividual trough plasminogen activity increase by an absolute 10 percentage points above baseline (Ryplazim trial 2).

Trial populationPediatric and adult patients with baseline plasminogen activity between <5% and 45% of normal and biallelic PLG mutations (n=15).

Dosing in trial6.6 mg/kg administered every 2 to 4 days for 48 weeks in the pivotal trial.

OpenPayer

Ryplazim (plasminogen, human-tvmh) — Indiana

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

Coding

Provider Actions and Requirements

Background

Definitions