CurrentEmblemHealthPolicy MG.MM.PH.430

Ziihera (zanidatamab-hrii) intravenous infusion

Clinical coverage criteria for use of Ziihera (zanidatamab-hrii) for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. Applies to EmblemHealth and ConnectiCare medical benefit review for preauthorization and renewal.

Policy Summary

PayerEmblemHealth

PolicyZiihera (zanidatamab-hrii) intravenous infusion

Policy CodePolicy MG.MM.PH.430

Change TypeNew policy

Effective DateFebruary 6, 2025

Next Review Date

Key ActionTreating physician must submit clinical evidence that the member meets all criteria (age, diagnosis, HER2 IHC3+ by FDA-approved/CLIA test, prior gemcitabine-containing regimen, LVEF status, pregnancy testing and contraception documentation) to EmblemHealth/ConnectiCare for preauthorization or post-payment review.

SourceLink

POLICY UPDATE CHANGES

New policy created for Ziihera (zanidatamab-hrii) with criteria and coding.

6Initial authorization length

2400Maximum dosing per label (mg q21d)

IHC 3+Required HER2 status

>=18Minimum patient age (years)

Medical Necessity Criteria for Ziihera (zanidatamab-hrii)

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Initial therapy — medically necessary

Covered when ALL of the following are met:

ALL of the following

Diagnosis of biliary tract cancer (gallbladder cancer or intra- or extra-hepatic cholangiocarcinoma) that is unresectable or metastatic
ICD-10 codes provided in code_groups
Patient is at least 18 years of age
Left ventricular ejection fraction (LVEF) is within normal limits prior to initiating therapy and will be assessed at regular intervals during treatment
LVEF monitoring required
No untreated or symptomatic central nervous system (CNS) metastases
Tumor is HER2-positive (IHC 3+) as determined by an FDA-approved or CLIA-compliant test
Females of childbearing potential must have a negative pregnancy test prior to the first dose and use effective contraception during therapy and for four months after last dose
Used as a single agent
Used as subsequent treatment after at least one prior line of therapy containing a gemcitabine-containing regimen

Continuation / Renewal criteria (ongoing coverage)

Coverage may be renewed when ALL of the following are met:

ALL of the following

Patient continues to meet the initial criteria and other relevant indication-specific criteria (e.g., performance status, concomitant therapy requirements)
Disease response or stabilization while on treatment (defined as stabilization of disease or decrease in size of tumor or tumor spread)
Absence of unacceptable toxicity from the drug (examples: left ventricular dysfunction including symptomatic congestive heart failure, severe infusion-related reactions, severe diarrhea)
LVEF criteria (within previous 3 months)
- LVEF has an absolute decrease of less than 16% from baseline

Length of authorization

Authorization duration and dosing limits

ALL of the following

Initial authorization length: 6 months
Max dose: 2400 mg every 21 days

Applicable Codes

Applicable HCPCS / Other procedure codesHCPCS|Other

J3590

Not otherwise classified, antineoplastic drugs

Applicable NDCsNDC

68727-0950-XX

Ziihera 300 mg lyophilized powder in a single-dose vial

Applicable ICD-10 diagnoses (biliary tract cancers)ICD-10Covered

C22.1	Intrahepatic bile duct carcinoma
C23	Malignant neoplasm of gallbladder
C24.0	Malignant neoplasm of extrahepatic bile duct
C24.8	Malignant neoplasm of overlapping sites of biliary tract
C24.9	Malignant neoplasm of biliary tract, unspecified

Authorization, Documentation, and Denial Risks

Prior Authorization

Preauthorization required with clinical documentation

The treating physician must submit to EmblemHealth (or ConnectiCare) clinical evidence that the member meets all policy criteria — including age, diagnosis of unresectable or metastatic biliary tract cancer, HER2 IHC3+ confirmed by an FDA‑approved or CLIA‑compliant test, prior receipt of at least one gemcitabine‑containing regimen, baseline LVEF status, and documentation of pregnancy testing and contraception — for preauthorization or for post‑payment review.

J3590
68727-0950-XX

Documentation Required

Cardiac monitoring and pregnancy testing

Document baseline LVEF within normal limits prior to initiating therapy and perform repeat LVEF assessments at regular intervals during treatment; for females of childbearing potential, document a negative pregnancy test prior to the first dose and counseling/use of effective contraception during therapy and for four months after the last dose.

Denial Risk

Denial risk for unmet criteria

Requests may be denied if the submission lacks required documentation of HER2 IHC3+ by an FDA‑approved or CLIA‑compliant test, lacks evidence of a prior gemcitabine‑containing regimen, documents untreated or symptomatic CNS metastases, or shows unacceptable cardiac function.

Clinical and Administrative Context

Ziihera (zanidatamab-hrii) is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA‑approved test and per the manufacturer's prescribing information.

EmblemHealth covers Ziihera with criteria. Treatment is limited to patients who meet all initial criteria: diagnosis of unresectable or metastatic biliary tract cancer (including gallbladder cancer or intra‑ or extra‑hepatic cholangiocarcinoma), age ≥ 18 years, tumor confirmed HER2 IHC 3+ by an FDA‑approved or CLIA‑compliant test, and used as a single agent after at least one prior line of therapy that included a gemcitabine‑containing regimen.

Cardiac function must be documented prior to initiation: baseline left ventricular ejection fraction (LVEF) must be within normal limits and will be reassessed at regular intervals during treatment. Continuation/renewal requires documented disease response or stabilization, absence of unacceptable toxicity (examples include left ventricular dysfunction or symptomatic congestive heart failure, severe infusion‑related reactions, severe diarrhea), and LVEF criteria within the previous 3 months — either an absolute decrease of <16% from baseline or LVEF >50% with an absolute decrease ≤10% from baseline.

For females of childbearing potential, a negative pregnancy test is required prior to the first dose and effective contraception must be used during therapy and for four months after the last dose.

EmblemHealth requires preauthorization with submission of clinical documentation (including age, diagnosis ICD‑10 code, HER2 IHC 3+ test results, prior gemcitabine‑containing regimen, baseline and follow‑up LVEF assessments, pregnancy testing and contraception counseling/use). Maximum dosing per label is 2400 mg every 21 days, and initial authorization is for 6 months.

Requests lacking required documentation (for example, absence of HER2 IHC 3+ confirmation, no prior gemcitabine‑containing regimen, untreated/symptomatic CNS metastases, or unacceptable cardiac function) may be denied.

Policy Summary

PayerEmblemHealth

PolicyZiihera (zanidatamab-hrii) intravenous infusion

Policy CodePolicy MG.MM.PH.430

Change TypeNew policy

Effective DateFebruary 6, 2025

Next Review Date

SourceLink

On This Page

OpenPayer

Ziihera (zanidatamab-hrii) intravenous infusion

Medical Necessity Criteria for Ziihera (zanidatamab-hrii)

Applicable Codes

Authorization, Documentation, and Denial Risks

Dosing, Authorization Length, and Renewal Thresholds

Clinical and Administrative Context

Defined Terms

Policy Changes