CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Ryplazim (plasminogen, human-tvmh) (Intravenous) — Coverage Criteria for Plasminogen Deficiency Type 1

Policy governs coverage and medical necessity criteria for Ryplazim intravenous therapy for members (Medicaid, Commercial, Medicare) with plasminogen deficiency type 1 treated or managed through Neighborhood Health Plan of Rhode Island.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyRyplazim (plasminogen, human-tvmh) (Intravenous) — Coverage Criteria for Plasminogen Deficiency Type 1

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective Date04/01/2022

Next Review DateN/A

Key ActionObtain prior authorization with documentation of baseline plasminogen activity ≤45% and hematology involvement; initial approval is for 12 weeks.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 wksinitial authorization period

6.6 mg/kgFDA dose

757 unitsmax units every 2 days

≤45%baseline threshold

E88.02covered ICD-10

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Coverage and Medical Necessity Criteria

Initial Therapy

Covered when ALL of the following are met

Initial Approval Criteria: Patient is at least 11 months of age; AND prescribed by or in consultation with a hematologist; AND patient blood pressure is controlled prior to initiation of treatment; AND patient has healing of lesions or wounds suspected as a source of a recent bleeding event prior to initiating therapy; AND baseline plasminogen activity measured prior to therapy and plasminogen activity level is ≤ 45% (allow a 7-day washout if receiving fresh frozen plasma); AND Ryplazim is dosed according to the FDA-labeled dosing for PLGD type 1 (initiate every 3 days at 6.6 mg/kg IV and adjust per trough plasminogen activity); AND Medicare members who have previously received Ryplazim within the past 365 days are exempt from Step Therapy Requirements.

Initiate therapy at every 3 days frequency

Renewal Therapy

Renewal/Continuation Criteria — Coverage renewed when

Renewal Criteria: Patient continues to meet the universal and other indication-specific relevant criteria (including concomitant therapy requirements and performance status); AND absence of unacceptable toxicity (e.g., severe bleeding, respiratory distress from tissue sloughing, hypersensitivity/anaphylaxis); AND patient has demonstrated a beneficial response (resolution of lesions) OR patient's lesions have not resolved after an initial 12 weeks of therapy OR there are new or recurrent lesions; AND patient may increase dosage frequency in one-day increments every 4-8 weeks up to every 2 days; AND re-assess trough plasminogen activity if, after 12 additional weeks of dose optimization, no clinical effect has been noted; AND if trough plasminogen activity is <10% above baseline, repeat trough and if low is confirmed AND no clinical effect, consider discontinuation;

Coverage renewed annually for complete responders; allow additional 12 weeks for dose optimization for less than complete response

Universal Criteria

Universal Monitoring Requirement

Monitoring: Patients with bleeding diatheses or on concomitant therapy with anticoagulants, antiplatelet drugs, or other agents which may interfere with normal coagulation will be monitored during and for 4 hours after infusion of Ryplazim.

No off‑label uses are covered beyond the FDA‑approved indication for plasminogen deficiency (PLGD) type 1. The manufacturer clinical summary and product warnings identify safety concerns providers must consider before initiating therapy, including the potential for worsened bleeding at lesion sites, tissue sloughing, risk of viral transmission with plasma‑derived products, development of neutralizing antibodies, and laboratory abnormalities. These risks underscore the requirement that Ryplazim be used according to the labeled indication and with appropriate specialist involvement and monitoring.

Requests will not meet medical necessity when required baseline testing, specialist involvement, or medical stability are missing. Specifically, coverage is contingent on documentation of a baseline plasminogen activity level ≤ 45% prior to therapy (a 7‑day washout is allowed if the patient received fresh frozen plasma), prescription by or consultation with a hematologist, and evidence that blood pressure is controlled and lesions/wounds suspected as the source of recent bleeding are healing prior to initiation. Absent these elements, authorization may be denied.

Additionally, dosing and monitoring requirements must be followed as specified (initiate at every 3 days and adjust per trough plasminogen activity). Failure to obtain required baseline or trough plasminogen activity measurements or to document hematology involvement and blood pressure control are explicit triggers for denial.

Billing and Diagnosis Codes

Covered HCPCS CodeHCPCSCovered

J2998

Injection, plasminogen, human-tvmh, 1 mg; 1 billable unit = 1 mg

NDCNDC

70573-0099-xx

Ryplazim 68.8 mg single-dose vial

Covered Diagnosis Codes (ICD-10)ICD-10Covered

E88.02

Plasminogen deficiency

Baseline plasminogen activity

Baseline thresholdBaseline plasminogen activity ≤ 45% prior to initiating Ryplazim therapy

FFP washout allowanceIf patient is receiving fresh frozen plasma, allow a 7‑day washout period before obtaining the baseline plasminogen activity level

Documentation requirementBaseline plasminogen activity must be measured and documented prior to therapy initiation

Trough plasminogen activity thresholds for dose frequency adjustment

Increase frequency (every 2 days)If trough plasminogen activity is <10% above baseline, change dosing frequency to every 2 days

Maintain frequency (every 3 days)

Authorization, Documentation, and Operational Requirements

Prior Authorization

Prior Authorization and Dosing

Prior authorization is required before initiation. Initial approval will be provided for 12 weeks. Dosing must follow the FDA‑labeled regimen for Ryplazim (6.6 mg/kg IV) with mg/kg calculations based on patient weight and individualized dosing frequency adjustments guided by plasminogen activity trough levels as described in dosing guidance.

Initial approval length: 12 weeks; renewals: annually for complete response or additional 12 weeks if less than complete response while optimizing frequency of administration
Dosing: Ryplazim 6.6 mg/kg IV — calculate dose from patient weight; initiate every 3 days and adjust frequency per trough plasminogen activity testing (see dosing criteria)
Baseline and monitoring labs required: baseline plasminogen activity prior to therapy (allow 7‑day washout if receiving fresh frozen plasma); obtain trough plasminogen activity ~72 hours after initial dose and prior to second dose to guide frequency adjustments

Documentation Required

Required Documentation

Background

Ryplazim (plasminogen, human‑tvmh) is a plasma‑derived human plasminogen product approved for treatment of congenital plasminogen deficiency (PLGD) type 1 (hypoplasminogenemia). The recommended dose for Type 1 PLGD is 6.6 mg/kg administered intravenously every 2 to 4 days, with initiation at every 3 days and adjustment of dosing frequency based on trough plasminogen activity measured about 72 hours after the initial dose. The pivotal approval was supported by a single‑arm, open‑label phase 2/3 study of 14 patients treated up to 48 weeks; common adverse reactions include headache, nasopharyngitis, gastrointestinal symptoms, and bleeding‑related events such as epistaxis and hematuria.

Definitions

Plasminogen deficiency type 1 — clinical summary

DefinitionPlasminogen deficiency (PLGD) type 1 (hypoplasminogenemia): an inherited condition characterized by low plasminogen activity leading to impaired fibrinolysis and formation of ligneous lesions

Indication for therapyRyplazim is approved for treatment of PLGD type 1 (hypoplasminogenemia)

Clinical consequencesCan impair tissue and organ function and cause visible lesions; lesions may be a source of bleeding

Evidence baseApproval based on a single‑arm, open‑label phase 2/3 study of 14 patients with treatment up to 48 weeks