CurrentMass General Brigham Health PlanPolicy N/A

Cinryze (C1 esterase inhibitor [human]) – Prophylaxis for Hereditary Angioedema

This policy governs prior authorization requirements for Cinryze as a pharmacy benefit for prophylaxis of hereditary angioedema (HAE) in Mass General Brigham Health Plan commercial/exchange members; it applies to specialty pharmacy dispensing.

Policy Summary

PayerMass General Brigham Health Plan

PolicyCinryze (C1 esterase inhibitor [human]) – Prophylaxis for HAE

Policy CodePolicy N/A

Change TypeMaterial revisions — benefit routing to pharmacy (specialty) and indication clarified to prophylaxis

Effective DateJan 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with diagnostic confirmation (C1‑INH laboratory or specified genetic/family history evidence) and required documentation including prescriber specialty and physician attestation for reauthorization.

SourceLink

POLICY UPDATE CHANGES

Updated policy to indicate it no longer applies to the medical benefit.

Diagnosis indication clarified from treatment to prophylaxis.

Removed requirement of prior use of generic Firazyr as that is only used for treatment.

6 monthsinitial approval and reauthorization duration

≥6 yrsminimum patient age for indication

Prior Authprogram type required

Pharmacy (specialty)

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benefit and dispensing requirement

Coverage Criteria for Cinryze (prophylaxis)

Initial Authorization Criteria

Covered when ALL of the following are met

Overall authorization requirements: 1) Use for prophylaxis of acute HAE attacks; 2) Not used in combination with any other HAE prophylactic; 3) Prescribed by or in consultation with an HAE specialist; AND 4) Diagnostic confirmation as specified below.

Diagnostic confirmation - C1-INH deficiency/dysfunction: Documentation that the member has C1 inhibitor deficiency or dysfunction confirmed by laboratory testing

Either antigenic C1-INH below the laboratory lower limit of normal OR normal antigenic C1-INH with low functional C1-INH (<50% or below the laboratory lower limit of normal).

Diagnostic confirmation - Normal C1-INH HAE: Documentation that the member has normal C1 inhibitor as confirmed by laboratory testing

Either a pathogenic mutation in F12, angiopoietin-1, plasminogen, KNG1, HS3ST6, or MYOF by genetic testing OR documented family history of angioedema plus angioedema refractory to a trial of high‑dose antihistamine (eg, cetirizine 40 mg/day or equivalent for ≥1 month).

Continuation Therapy

Reauthorization will be granted when ALL of the following are met

Continuation of therapy: 1) Member continues to meet initial approval criteria; 2) Physician attestation that the member has experienced a reduction in severity and/or duration of acute HAE attacks (eg, ≥ 50%) since starting treatment.

For members who are new to the plan (enrolled within the past 90 days), prior authorization may be granted only if there is documentation that the member is currently receiving the requested medication. Note that this 90-day grandfathering provision does not apply when the product was obtained solely as samples or through the manufacturer's patient assistance program; such situations are excluded and may result in denial if active-treatment documentation is not provided.

Requests for use of Cinryze for routine prophylaxis of hereditary angioedema must not be for concomitant use with any other medication intended for HAE prophylaxis. Use of Cinryze in combination with another prophylactic HAE agent is not allowed and does not meet medical necessity criteria.

Benefit and Coding / Dispensing

Pharmacy benefit / specialty dispensingNDC

NDC (not listed)

Cinryze dispensed at specialty pharmacy per pharmacy benefit (document notes specialty but no NDC provided)

Clinical response threshold for reauthorization

Reauthorization clinical response thresholdPhysician attestation of reduction in severity and/or duration of acute HAE attacks (e.g., ≥ 50%) since starting treatment

Reauthorization intervalReauthorization granted when member continues to meet initial approval criteria and attests to clinical response

Required documentation for reauthorizationPhysician attestation documenting ≥50% improvement in severity and/or duration of attacks

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required for Cinryze under the pharmacy benefit (specialty) for Commercial/Exchange members. This medication is designated specialty and must be filled at a contracted specialty pharmacy.

Applies to Commercial/Exchange members under the pharmacy (specialty) benefit
Specialty pharmacy fulfillment required

Step Therapy

No step therapy requirements specified for Cinryze. Prior Firazyr prior-use requirement was removed.

Documentation Required

Background

Hereditary angioedema (HAE) is a condition managed in part by replacement of C1 esterase inhibitor (C1‑INH) to reduce the frequency and severity of angioedema attacks. Cinryze (C1 esterase inhibitor [human]) is indicated for routine prophylaxis of HAE in patients aged ≥ 6 years. Prior authorization under the pharmacy benefit (specialty dispensing) is required for Cinryze, and reauthorization requires documentation that the member continues to meet initial criteria plus a physician attestation of clinical benefit (for example, a ≥ 50% reduction in severity and/or duration of acute attacks).

Definitions and Diagnostic Criteria

C1-INH deficiency or dysfunction — diagnostic thresholds

Definition – low antigenic C1-INHC1 inhibitor (C1-INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test

Definition – low functional C1-INHC1-INH functional level less than 50% or below the laboratory lower limit of normal

Diagnostic requirementLaboratory confirmation of C1-INH deficiency or dysfunction required for initial authorization (either low antigenic OR low functional level)

HAE with normal C1-INH — diagnostic confirmation

Genetic confirmationPathogenic mutation in F12, angiopoietin-1, plasminogen, KNG1, HS3ST6, or MYOF confirmed by genetic testing

Family history plus treatment refractoryDocumented family history of angioedema plus refractory to high‑dose antihistamine trial (cetirizine 40 mg/day or equivalent for ≥1 month)

Policy Summary

PayerMass General Brigham Health Plan

PolicyCinryze (C1 esterase inhibitor [human]) – Prophylaxis for HAE

Policy CodePolicy N/A

Change TypeMaterial revisions — benefit routing to pharmacy (specialty) and indication clarified to prophylaxis

Effective DateJan 1, 2026

Next Review DateN/A

SourceLink

On This Page

Required Documentation

Documentation must include laboratory confirmation or genetic/family history evidence as specified for hereditary angioedema (HAE).

Lab confirmation of C1 inhibitor deficiency or dysfunction: C1-INH antigenic level below lab lower limit of normal OR normal antigenic level with C1-INH functional level <50% or below lab lower limit of normal
Genetic testing documenting F12, angiopoietin-1, plasminogen, KNG1, HS3ST6, or MYOF mutation when C1-INH levels are normal
Alternatively, documented family history of angioedema plus prior trial of high‑dose antihistamine (e.g., cetirizine 40 mg/day or equivalent) for ≥1 month showing refractory symptoms
Prescriber is a specialist in HAE or treatment is in consultation with an HAE specialist
For continuation: physician attestation of ≥50% reduction in severity and/or duration of acute attacks since starting treatment

Denial Risk

Denial Triggers

Requests will be denied if diagnostic confirmation for C1‑INH deficiency/dysfunction or the specified genetic/family history criteria are not met, or if the medication is intended to be used in combination with another prophylactic HAE agent.

Denial triggers include lack of laboratory evidence of C1‑INH deficiency/dysfunction (per lab definitions)
Denial if neither genetic testing confirming specified mutations nor documented family history with refractory response to high‑dose antihistamine trial is provided when C1‑INH levels are normal
Denial if request indicates concurrent use with another prophylactic HAE medication

Denial Risk

Denial Triggers for New‑to‑Plan Members

For members new to the plan (within the past 90 days), authorization may be granted only if the member is currently receiving the requested medication and supply was not obtained solely via samples or a manufacturer's patient assistance program.

Exclusion: members who only received samples or supply through manufacturer patient assistance programs are not eligible for new‑to‑plan authorization
Requirement: documentation that member is actively receiving the medication (not limited to samples/PAP)

ApplicabilityNormal C1-INH on laboratory testing plus one of the above (genetic mutation OR family history with refractory response) meets diagnostic criteria for HAE with normal C1-INH