CurrentMass General Brigham Health PlanPolicy N/A

Cinryze (C1 esterase inhibitor [human]) — Coverage Criteria

Policy governing prior authorization, specialty dispensing, quantity limits, and medical benefit requirements for Cinryze used as prophylaxis for hereditary angioedema (HAE) for Mass General Brigham Health Plan members.

Policy Summary

PayerMass General Brigham Health Plan

PolicyCinryze (C1 esterase inhibitor [human]) — Coverage Criteria

Policy CodePolicy N/A

Change TypeRevised indicationStep therapy removed

Effective DateJan 1, 2024

Next Review DateN/A

Key ActionSubmit prior authorization with documentation confirming C1‑INH deficiency or genetic testing and specialist involvement.

SourceLink

POLICY UPDATE CHANGES

Diagnosis indication language changed from treatment to prophylaxis.

Removed requirement of prior use of generic Firazyr.

6 monthsinitial and reauthorization approval length

>=6 yminimum patient age for indication

specialtymedication designation

prior authauthorization requirement

Coverage Criteria for Cinryze (C1 esterase inhibitor [human])

Diagnostic Confirmation (ANY one required)

Diagnostic Confirmation — Authorization requires ANY one of the following laboratory or genetic confirmations of HAE:

ANY of the following

C1 inhibitor (C1-INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test.
Normal C1-INH antigenic level with low C1-INH functional level (C1-INH functional less than 50% or below the lower limit of normal as defined by the laboratory performing the test).
Documented pathogenic or likely pathogenic mutation in a known HAE-associated gene (e.g., SERPING1, F12, PLG, ANGPT1, KNG1, HS3ST6, MYOF) confirmed by genetic testing.
Normal C1-INH levels with clinical phenotype and documented family history of angioedema plus angioedema refractory to a trial of high‑dose antihistamine therapy (e.g., cetirizine 40 mg daily or equivalent) for at least one month; used when laboratory evidence of C1-INH deficiency/dysfunction is not present but hereditary angioedema is suspected (type III/HAE with normal C1-INH).

Policy Summary

PayerMass General Brigham Health Plan

PolicyCinryze (C1 esterase inhibitor [human]) — Coverage Criteria

Policy CodePolicy N/A

Change TypeRevised indicationStep therapy removed

Effective DateJan 1, 2024

Next Review DateN/A

Key ActionSubmit prior authorization with documentation confirming C1‑INH deficiency or genetic testing and specialist involvement.

SourceLink

On This Page

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Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Cinryze. Authorization may be granted for members new to the plan who are currently receiving Cinryze at the time of enrollment (excludes product obtained as samples or via manufacturer's patient assistance programs).

Applies to prophylactic use of Cinryze for Hereditary Angioedema (HAE).
New members already receiving Cinryze may be authorized; samples and patient assistance program supplies are excluded.

Note

Policy Change — Prior Use of Generic Firazyr Removed

The requirement for prior use of generic Firazyr has been removed from the policy. This was a material policy change effective 2024-01-01.

Prior step requiring trial of generic Firazyr for treatment was removed because Firazyr is used for treatment rather than prophylaxis.

Documentation Required

Documentation Required — Confirmation of C1‑INH Deficiency or Dysfunction

Provider must submit documentation confirming C1-INH deficiency or dysfunction. Documentation may include laboratory testing results or genetic testing as described in the coverage criteria.

Acceptable laboratory evidence: low C1-INH antigenic level below the laboratory's lower limit of normal, or normal antigenic level with low functional C1-INH (functional C1-INH <50% or below lab lower limit).
Acceptable genetic evidence: documented pathogenic mutation (eg, F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF) confirmed by genetic testing.
If C1-INH is normal, documentation must show family history of angioedema and refractory response to high‑dose antihistamine trial (eg, cetirizine 40 mg daily or equivalent for ≥1 month).

Denial Risk

Denial Risk — Insufficient Indication or Documentation

Denial may be triggered if the requested use is not for prophylaxis of HAE attacks or if submitted documentation is insufficient to confirm C1‑INH deficiency/dysfunction per the coverage criteria.

Requests for indications other than prophylaxis of acute HAE attacks are not covered under this authorization pathway.
Insufficient documentation includes absence of appropriate lab results, genetic testing, or required attestation by a specialist when indicated.

Definitions

C1‑INH functional deficiency — threshold definition

DefinitionC1-INH functional deficiency is defined as C1-INH functional level less than 50% or C1-INH functional level below the lower limit of normal as defined by the laboratory performing the test.

Laboratory referenceThreshold may be reported either as a percent (<50%) or relative to the laboratory's lower limit of normal; either meets the definition.

Use in authorizationDocumentation of low C1-INH functional level is an acceptable diagnostic confirmation for HAE prophylaxis criteria.

HAE with normal C1‑INH and pathogenic mutation — listed genes

Included pathogenic mutationsF12; angiopoietin-1; plasminogen; kininogen-1 (KNG1); HS3ST6 (heparan sulfate glucosamine 3-O-sulfotransferase 6); MYOF (myoferlin).

Confirmation methodPathogenic gene mutation must be confirmed by genetic testing as documentation for HAE with normal C1-INH.

Context of useListed mutations apply when C1-INH antigenic level is normal but clinical suspicion for HAE persists; genetic confirmation satisfies diagnostic criteria.

OpenPayer

Cinryze (C1 esterase inhibitor [human]) — Coverage Criteria

Coverage Criteria for Cinryze (C1 esterase inhibitor [human])

Provider Actions, Prior Authorization, and Documentation Requirements

Background

Definitions