Zanidatamab-hrii (Ziihera) — CPB 1075 | AETNA Coverage Update

Aetna modified CPB 1075 for zanidatamab-hrii (Ziihera), effective December 20, 2025. Here's what billing teams need to know before submitting claims.

Aetna, a CVS Health company, updated its zanidatamab-hrii (Ziihera) coverage policy under CPB 1075 Aetna system. This policy governs commercial plan coverage for J9276 (injection, zanidatamab-hrii, 2 mg) — a HER2-targeted bispecific antibody for biliary tract cancers. The update defines exactly one covered indication, locks down prior authorization requirements, and draws a hard line around everything else. If your team bills J9276 or pairs it with CPT 96413 and 96415 for IV infusion administration, this policy directly affects your reimbursement.

Quick-Reference Table

Aetna Zanidatamab-hrii Coverage Criteria and Medical Necessity Requirements 2025

The Aetna zanidatamab-hrii coverage policy under CPB 1075 is narrow by design. Aetna considers zanidatamab-hrii (Ziihera) medically necessary for exactly one indication: subsequent treatment of unresectable or resected gross residual (R2) disease or metastatic HER2-positive (IHC 3+) biliary tract cancer as a single agent.

That phrase "subsequent treatment" matters. Confirm with Aetna during precertification what prior treatment history is required to satisfy this criterion before submitting.

The covered cancer types are intrahepatic cholangiocarcinoma (C22.1), extrahepatic cholangiocarcinoma (C24.0), and gallbladder cancer (C23). Overlapping biliary tract sites (C24.8) and unspecified biliary tract malignancy (C24.9) are also mapped in the policy. The policy requires HER2 positivity confirmed at IHC 3+. No alternative HER2 testing pathways are specified in this policy.

Prior Authorization Requirements

Precertification is mandatory for all Aetna participating providers and members in applicable plan designs. Call (866) 752-7021 or fax (888) 267-3277 to initiate precertification. Statement of Medical Necessity forms are available through Aetna's Specialty Pharmacy Precertification portal.

Do not submit J9276 claims without confirmed prior authorization in place. Specialty oncology drugs of this class typically represent significant reimbursement exposure — a denial requires prompt appeal.

Continuation of Therapy

Aetna will approve reauthorization when two conditions are met: the member is receiving treatment for a covered indication, and there is no evidence of unacceptable toxicity or disease progression. Document disease status and tolerability at every reauthorization cycle. Missing either element in the chart will stall reauthorization and delay treatment.

Aetna Zanidatamab-hrii Exclusions and Non-Covered Indications

Aetna is explicit here: all indications other than the single biliary tract cancer indication described above are considered experimental, investigational, or unproven.

That's a broad exclusion. Zanidatamab is being studied in HER2-positive gastroesophageal cancers, breast cancer, and other solid tumors. None of those indications are covered under this commercial coverage policy. If a clinician prescribes Ziihera for a gastric cancer patient or a breast cancer patient, the claim will not pass medical necessity review under CPB 1075.

If your practice is treating patients on clinical trials involving zanidatamab for off-label indications, route those claims through your trial billing pathways — not standard commercial billing under J9276.

Coverage Indications at a Glance

Aetna Zanidatamab-hrii Billing Guidelines and Action Items 2025

These are the steps your team needs to complete now — before the effective date of December 20, 2025 has passed you.

CPT, HCPCS, and ICD-10 Codes for Zanidatamab-hrii Under CPB 1075

Covered HCPCS Code (When Selection Criteria Are Met)

Key ICD-10-CM Diagnosis Codes

A Note on the Premedication Code List

One thing worth flagging: the premedication list in CPB 1075 includes J2357 (omalizumab) and J2786 (reslizumab). These are monoclonal antibodies used for allergic conditions and eosinophilic asthma — not typical infusion premedication agents. Their inclusion as "related codes" in this policy likely reflects a template-based approach to listing supportive care agents rather than a clinical expectation that they'll be administered before zanidatamab infusions.

Bill them only if they were actually administered and documented. Don't treat their presence in the policy code list as permission to add them to a standard zanidatamab billing template. That's how you get a claim denial — or worse, a post-payment audit.