CurrentColorado Rocky Mountain Health PlansPolicy 2026D0070H

Ryplazim (plasminogen, human-tvmh)

Policy governs medical benefit coverage criteria for Ryplazim (plasminogen, human-tvmh) for treatment of plasminogen deficiency type 1 (hypoplasminogenemia) under UnitedHealthcare Commercial plans; affects providers prescribing/administering Ryplazim.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRyplazim (plasminogen, human-tvmh)

Policy CodePolicy 2026D0070H

Change TypeNo material changes

Effective DateMar 1, 2026

Next Review Date

Key ActionObtain prior authorization with documented diagnosis, plasminogen activity ≤ 45%, prescriber specialty (hematologist or consult), and dosing per FDA labeling.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≤45%plasminogen activity threshold

12initial auth (mo)

J2998HCPCS

6.6 mg/kgtrial dose

78%/75%lesion resolution (48w)

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Initial Therapy — Ryplazim

Ryplazim is proven and medically necessary when ALL of the following are met:

Initial therapy criteria: Diagnosis of hypoplasminogenemia as measured by plasminogen activity level ≤ 45% of laboratory standard; presence of clinical signs and symptoms of the disease (e.g., ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing, etc.); prescribed by or in consultation with a hematologist; dosing in accordance with United States Food and Drug Administration–approved labeling; initial authorization for no more than 12 months.≤ 45% plasminogen activity

Prescriber specialty required; dosing per FDA labeling; authorization limit 12 months

Continuation (Reauthorization) Therapy — Ryplazim

Continuation is proven and medically necessary when ALL of the following are met:

Continuation therapy criteria: Patient has previously received Ryplazim therapy; patient experienced a positive clinical response to Ryplazim (examples: reduction in lesion number/size, improved wound healing, or plasminogen activity trough level increased by at least 10 percentage points from baseline); prescribed by or in consultation with a hematologist; dosing in accordance with United States Food and Drug Administration–approved labeling; reauthorization for no more than 12 months.≥ 10 percentage point increase in trough plasminogen activity as example of response

Positive clinical response may be clinical or laboratory-based

Not Medically Necessary — Ryplazim

Not Medically Necessary: Use of Ryplazim for the treatment of idiopathic pulmonary fibrosis.

Explicitly stated as unproven and not medically necessary

Treatment of idiopathic pulmonary fibrosis with Ryplazim is excluded; this use is considered unproven and not medically necessary.

Ryplazim is unproven and not medically necessary for the treatment of idiopathic pulmonary fibrosis.

Applicable Codes and Diagnostic Thresholds

Applicable HCPCS and ICD-10 Codesmixed

J2998	Injection, plasminogen, human-tvmh, 1 mg
E88.02	Plasminogen deficiency

Plasminogen activity for diagnosis and trial baseline

Policy diagnostic thresholdPlasminogen activity level ≤ 45% of laboratory standard

Trial enrollment baseline rangeBaseline plasminogen activity in pivotal trial: <5% to 45% of normal

Required clinical documentation for initiationPresence of clinical signs/symptoms (e.g., ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing)

Authorization duration (initial and reauthorization)Initial and reauthorization limited to no more than 12 months

Prescriber requirementPrescribed by or in consultation with a hematologist

Provider Requirements, Documentation, and Billing

Prior Authorization

Prior Authorization Required

Prior authorization is required for Ryplazim (plasminogen, human-tvmh). Requests must document diagnosis, laboratory confirmation of plasminogen activity ≤ 45% of laboratory standard, prescriber specialty or consultation, and dosing consistent with FDA labeling. Initial authorizations are limited to 12 months.

Diagnosis: plasminogen deficiency type 1 (hypoplasminogenemia).
Lab: plasminogen activity ≤ 45% of laboratory standard.
Prescriber: prescribing clinician must be a hematologist or the request must include documentation of consultation with a hematologist.
Authorization length: initial authorization ≤ 12 months.

Step Therapy

Step Therapy / Prescriber Requirement

No step therapy is required prior to coverage. However, prescriber requirement applies: therapy must be prescribed by or in consultation with a hematologist.

Step therapy: none required.
Prescriber requirement: prescribing clinician must be a hematologist or include hematology consultation documentation.

Documentation Required

Required Documentation

Document the clinical rationale for therapy and supporting laboratory and response data. Maintain records showing presence of clinical signs or symptoms, baseline and subsequent plasminogen activity levels, and evidence of clinical benefit for reauthorization.

Clinical signs/symptoms consistent with hypoplasminogenemia (e.g., ligneous conjunctivitis, gingivitis, tonsillitis, abnormal wound healing, etc.).
Baseline plasminogen activity ≤ 45% and numeric lab values (report lab reference ranges).
For continuation: evidence of positive clinical response (e.g., reduction in lesion number/size, improved wound healing, or plasminogen activity trough increase ≥ 10 percentage points from baseline).
Documentation of hematologist prescribing or consultation.
Dosing and schedule consistent with FDA-approved labeling.

Billing Rule

Billing Documentation

Billing should reference the HCPCS code for plasminogen, human-tvmh and include supporting clinical documentation on the claim as applicable.

HCPCS: J2998 — Injection, plasminogen, human-tvmh, 1 mg
Include prior authorization number on claims where required and retain clinical documentation supporting medical necessity.

Denial Risk

Triggers for Denial

Denials may be issued if required clinical or laboratory documentation is missing or if the indication is not supported by policy (including use for idiopathic pulmonary fibrosis).

Possible triggers for denial: absence of documented plasminogen activity ≤ 45%.
Possible triggers for denial: lack of documented clinical signs or symptoms of plasminogen deficiency type 1.
Not medically necessary: use of Ryplazim for idiopathic pulmonary fibrosis — such requests will be denied.

Background on Plasminogen and Indication

Plasminogen is a liver-synthesized precursor protein that is converted to plasmin, the primary enzyme responsible for fibrin clot lysis and tissue remodeling. Deficiency of plasminogen (plasminogen deficiency type 1, or hypoplasminogenemia) is a rare autosomal-recessive fibrinolytic disorder characterized by low plasminogen levels and the accumulation of extravascular, fibrin-rich "ligneous" pseudomembranous lesions on mucous membranes (for example, conjunctiva, gums, respiratory and genital tracts).

Replacement therapy with Ryplazim aims to restore plasminogen activity, reduce or resolve ligneous lesions, and improve related functional impairments. Clinical evaluation and the policy require documentation of plasminogen activity (policy threshold: ≤ 45% of laboratory standard) and clinical signs or symptoms consistent with hypoplasminogenemia to establish the diagnosis and baseline for treatment.

Definitions and Condition Description

Plasminogen deficiency type 1 (hypoplasminogenemia)

DefinitionA rare autosomal-recessive fibrinolytic disorder characterized by low plasminogen levels leading to abnormal extravascular accumulation of fibrin-rich ligneous pseudomembranous lesions on mucous membranes

Common clinical manifestationLigneous conjunctivitis: inflamed, woody growth on conjunctival membranes that can cause visual impairment or blindness if untreated

Other affected sitesMucous membranes throughout the body including gums, respiratory and genital tracts (lesions may be external or internal)

PathophysiologyDeficiency of plasminogen impairs conversion to plasmin and fibrin clot/lesion breakdown, allowing accumulation of fibrin-rich lesions

Therapeutic implicationReplacement therapy can increase plasma plasminogen levels and reduce extravascular fibrinous lesions

OpenPayer

Ryplazim (plasminogen, human-tvmh)

Coverage Criteria for Ryplazim (plasminogen, human-tvmh)

Applicable Codes and Diagnostic Thresholds

Provider Requirements, Documentation, and Billing

Background on Plasminogen and Indication

Definitions and Condition Description