Ziihera (J9276) Billing & Coding Guide | Zanidatamab

Phase 1 Identify what you're billing Confirm HER2 IHC 3+ from an FDA-approved companion diagnostic before any other coding. HER2 IHC 2+ is NOT eligible — even with ISH amplification.

Dosing & unit math FDA label verified May 2026

From the FDA prescribing information for Ziihera (zanidatamab-hrii), November 2024 accelerated approval.

Adult dosing

20 mg/kg IV every 2 weeks (q14d), weight-based
Calculate total dose using actual body weight
Continue until disease progression or unacceptable toxicity
First infusion: 60 minutes. Observe during and after first infusion for infusion-related reactions.
Subsequent infusions: 30 minutes if first dose tolerated
If a planned dose is missed, administer the next dose as soon as possible and resume the q14d schedule

Preparation

Each 300 mg single-dose vial is a lyophilized cake/powder — reconstitute with 6 mL Sterile Water for Injection to yield 50 mg/mL clear to slightly opalescent, colorless to brownish-yellow solution.
Gently swirl until completely dissolved; do not shake. Inspect for particulates.
For a 70 kg patient (1400 mg dose), reconstitute 5 vials = 1500 mg drawn (100 mg waste); withdraw 28 mL of reconstituted solution.
Further dilute calculated dose in 250 mL of 0.9% Sodium Chloride Injection only — per label, do NOT use 5% Dextrose.
Mix by gentle inversion. Final infusion solution may be stored at room temperature for up to 6 hours or refrigerated up to 24 hours.
Administer through a dedicated IV line using a 0.2 or 0.22 micron in-line, low-protein-binding filter per current PI.

Premedication for infusion-related reactions

First dose (and as needed for subsequent): antihistamine (e.g., diphenhydramine), antipyretic (e.g., acetaminophen), and corticosteroid (e.g., dexamethasone) per institutional protocol
If a Grade 1 or 2 infusion-related reaction occurs, premedicate before all subsequent infusions; consider extending infusion time
For Grade 3 reaction: hold, treat, restart at slower rate after recovery; for Grade 4: permanently discontinue

Worked example — 70 kg patient, standard 20 mg/kg dose

# Per-dose math (weight-based) Patient weight: 70 kg Dose: 70 \times 20 = 1400 mg Vials needed: 1400 / 300 = 4.67 \to 5 vials drawn (1500 mg total drawn) Drug administered: 1400 mg = 1400 / 2 = 700 units (J9276 + JZ) Drug wasted: 1500 - 1400 = 100 mg = 50 units (J9276 + JW — separate line) Admin: 96413 (first 60 min, single substance); subsequent 30-min infusions still bill 96413 (no 96415 needed unless infusion extends past 1 hr) # Per cycle (one infusion every 14 days) Doses per cycle: 1 infusion q14d Drug units billed per cycle (admin): 700 + 50 JW = 750 total paid units # Year-1 (~26 cycles) Total infusions: 26 (q14d \times 52 wk = 26 doses/year) Total drug units administered: ~18,200 units (admin) + ~1,300 units (JW) = ~19,500 total paid units Total drug cost (Q2 2026 ASP+6%): ~$487,422 administered + ~$32,495 JW = ~$519,917 before sequestration After ~2% sequestration: ~$509,518 actual paid

Why JW is the rule for Ziihera: The 300 mg vial size rarely divides evenly into the calculated weight-based dose. For most patients (50–110 kg), the dose lands between two vial multiples, requiring rounding up to the next vial. The discarded portion (single-dose vial waste) must be billed on a separate JW line. Standard 750 mg-flat-dose drugs like Bizengri have zero waste; Ziihera almost always has some.

Dose-rounding policy: Per JazzCares billing guide and most payers, do NOT round the calculated dose down to fit vial multiples (e.g., do not give 1200 mg instead of 1400 mg). Always administer the full calculated 20 mg/kg dose; document any deviation in the chart. Some institutional protocols round to nearest 50 mg — align with your pharmacy's policy and document on the claim.

NDC reference FDA NDC Directory verified May 2026

NDC	Strength	Package Size	Units/Vial
`68727-950-01` / `68727-0950-01`	300 mg lyophilized powder (reconstitutes to 50 mg/mL)	Single-vial carton — 1 vial per carton	150 units (1 unit = 2 mg)
`68727-950-02` / `68727-0950-02`	300 mg lyophilized powder (reconstitutes to 50 mg/mL)	2-vial carton	300 units per carton

Verify 11-digit NDC format on current DailyMed label. Submit the 11-digit carton NDC with the N4 qualifier on the claim line. Vial-level NDC will trigger denial. For a typical 1400 mg dose (5 vials), bill NDC quantity reflecting total mL of reconstituted solution drawn (28 mL) under unit-of-measure ML.

NDC unit-of-measure reminder: Ziihera is a lyophilized powder requiring reconstitution. Each 300 mg vial reconstitutes to 6 mL of 50 mg/mL solution. NDC quantity on the claim should reflect total mL of reconstituted solution drawn from vials (not mg, not units). For a 1400 mg dose (5 vials drawn), 28 mL administered + 2 mL discarded = total 30 mL prepared — report mL drawn per your MAC's preferred convention.

HER2 IHC 3+ testing — the universal coverage gate NCCN / payer policies verified May 2026

Ziihera coverage is gated entirely on documented HER2 IHC 3+ from an FDA-approved companion diagnostic. This is the single highest-yield piece of documentation for PA approval and the #1 denial driver when missing.

HER2 overexpression in biliary tract cancer occurs in roughly 5–20% of cases overall — highest in gallbladder carcinoma (10–20%), intermediate in extrahepatic cholangiocarcinoma (~10%), and lower in intrahepatic cholangiocarcinoma (~5%). Unlike breast and gastric cancer where HER2 IHC is reflexive on most specimens, HER2 testing in BTC is not historically routine — many archival BTC specimens were never tested and require retroactive IHC on the original surgical or biopsy block.

FDA-approved companion diagnostic

VENTANA PATHWAY anti-HER2/neu (4B5) assay (Roche Tissue Diagnostics) — FDA-approved companion diagnostic for Ziihera. Validated for BTC scoring.
Other FDA-approved HER2 IHC kits validated in BTC may be acceptable per payer policy — confirm with PA reviewer.
Testing should be performed on a CAP/CLIA-accredited pathology laboratory.

HER2 IHC scoring (BTC-specific criteria)

IHC 3+ (eligible for Ziihera): intense complete or basolateral or lateral membranous reactivity in >10% of tumor cells
IHC 2+ (NOT eligible): weak-to-moderate complete or basolateral or lateral membranous reactivity in >10% of tumor cells — even with ISH amplification, IHC 2+ patients are NOT included in the FDA-approved indication
IHC 1+ or 0 (NOT eligible): faint or no membranous staining

HER2 ISH (FISH/DDISH) — NOT required

Unlike breast and gastric cancer where IHC 2+ tumors reflex to ISH for amplification confirmation, Ziihera coverage is gated only on IHC 3+ status. ISH amplification testing is NOT required for Ziihera coverage when IHC is 3+, and IHC 2+ tumors are NOT eligible regardless of ISH result. This is a binary gate: IHC 3+ qualifies; everything else does not.

Documentation for PA submission: include the full surgical or biopsy pathology report showing (1) IHC score (3+ binary), (2) antibody clone (typically 4B5 from VENTANA PATHWAY), (3) staining pattern (intensity + percent of tumor cells), (4) testing methodology and lab CAP/CLIA accreditation, (5) report date and ordering pathologist. Most payers will not approve based on a chart note of "HER2 positive" alone without the pathology report.

Archival tissue retrieval is common. Many BTC patients were not HER2-tested at original diagnosis. Pathology labs can typically perform retrospective IHC on archival FFPE blocks (typically 1–2 week turnaround). Coordinate with pathology early to avoid PA delays. If the original biopsy was small, repeat biopsy may be required — document medical necessity in chart.

Phase 2 Code the claim Chemo admin codes apply. JW + JZ both lines required on most claims (300 mg vial size rarely matches weight-based dose).

Administration codes CPT verified May 2026

Ziihera is a therapeutic monoclonal antibody for cancer treatment — chemotherapy administration codes are correct per AMA classification.

Code	Description	When to use
`96413`	Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug	Primary code for every Ziihera infusion. Covers the first 60 minutes of the infusion. Standard first dose (60 min) and subsequent dose (30 min) both bill 96413 as the primary code.
`96415`	Chemotherapy administration, IV infusion; each additional hour	Not typically needed for routine Ziihera infusions. Only required if the infusion clinically extends past 60 minutes (e.g., infusion-reaction-driven slowdown). Most encounters bill 96413 alone.
`96365` / `96366`	Therapeutic IV infusion (non-chemo)	NOT appropriate. Ziihera is an antineoplastic agent and chemotherapy administration codes apply per AMA classification.
`96360` / `96361`	Hydration IV	Bill separately if IV hydration administered alongside infusion. Use modifier 59 / X-modifier as appropriate.

Infusion-time math: Standard first-dose 60-minute infusion bills 96413 × 1 (no 96415 needed — the first 60 min is included). Subsequent 30-minute infusions also bill 96413 × 1 (single substance, single hour or less). Document actual infusion start/stop times — CMS audits look for chair-time documentation matching billed units. Only add 96415 if reactions slow the infusion past 60 minutes.

96415 unit cap awareness: Many MACs limit 96415 to a maximum of 8 units per encounter. Routine Ziihera infusions do not approach this; combination with other long infusions on the same day may — verify same-day chemo regimens.

Modifiers CMS verified May 2026

JW + JZ — both lines on most Ziihera claims

Effective July 1, 2023, CMS requires either JZ (no waste) or JW (drug discarded from a single-dose container) on every J9276 claim. Because Ziihera is dosed weight-based at 20 mg/kg and supplied in 300 mg single-dose vials, the calculated dose rarely divides evenly into vial multiples — most patients require one JZ line (administered) + one JW line (discarded) on the same encounter.

Standard 1400 mg dose (70 kg patient): 5 vials × 300 mg = 1500 mg drawn; 1400 mg administered + 100 mg discarded → J9276-JZ × 700 units AND J9276-JW × 50 units on separate claim lines.
Edge case — 90 kg patient: 90 × 20 = 1800 mg = exactly 6 vials × 300 mg = 1800 mg drawn = 1800 mg administered, zero waste → J9276-JZ × 900 units only; no JW.
Both lines must reconcile against total mg drawn from vials: JZ units + JW units = (vials × 300) ÷ 2.

Worked example — 70 kg patient (1400 mg dose)

# Vials and waste (1400 mg dose, 70 kg patient) Calculated dose: 70 kg \times 20 mg/kg = 1400 mg Vials drawn: ceil(1400 / 300) = 5 \times 300 mg = 1500 mg total drawn Administered: 1400 mg = 700 units \to J9276-JZ Discarded: 100 mg = 50 units \to J9276-JW (separate line) # Claim lines (first dose) Line 1: J9276-JZ \times 700 units Line 2: J9276-JW \times 50 units Line 3: 96413 \times 1 (chemo IV, first 60 min — first dose 60-min infusion) # Claim lines (subsequent dose, 30-min infusion) Line 1: J9276-JZ \times 700 units Line 2: J9276-JW \times 50 units Line 3: 96413 \times 1 (chemo IV, single substance, 30 min \leq 1 hr)

Worked example — 90 kg patient (1800 mg dose, zero waste)

# Vials and waste (1800 mg dose, 90 kg patient) Calculated dose: 90 kg \times 20 mg/kg = 1800 mg Vials drawn: 1800 / 300 = exactly 6 \times 300 mg = 1800 mg total drawn Administered: 1800 mg = 900 units \to J9276-JZ Discarded: 0 mg = 0 units \to no JW line # Claim lines Line 1: J9276-JZ \times 900 units Line 2: 96413 \times 1 (chemo IV admin)

Common error #1: Forgetting the JW line when waste occurred. With Ziihera's 300 mg vial and weight-based dosing, JW applies on the majority of claims. Audit your pharmacy's actual draw versus administered mg before submitting JZ-only.

Common error #2: Unit math error from the 2 mg = 1 unit convention. Total mg ÷ 2 = units (not mg = units like Bizengri J9382). A 1400 mg dose is 700 units, not 1400 units. Doubling units is a high-frequency error that triggers payment-limit denials or audit flags.

Modifier 25 — same-day E/M

Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the infusion (e.g., LVEF assessment review, toxicity-driven dose modification decision, infusion-reaction management, diarrhea workup). Routine pre-infusion clinical assessment is bundled.

340B modifiers (JG, TB)

For 340B-acquired Ziihera, follow your MAC's current 340B modifier policy. As of May 2026, JG (340B-acquired, normal payment) and TB (340B-acquired, informational) policy varies by region; verify with your MAC.

ICD-10-CM by indication FY2026 verified May 2026

Use the most specific code supported by encounter documentation; ICD-10 alone is never sufficient for PA approval — the HER2 IHC 3+ pathology report must accompany the submission.

Indication	Primary ICD-10	Required supporting documentation
Advanced unresectable / metastatic HER2+ (IHC 3+) intrahepatic cholangiocarcinoma	`C22.1` (intrahepatic bile duct carcinoma)	HER2 IHC 3+ pathology report (VENTANA PATHWAY 4B5 or equivalent FDA-approved companion diagnostic); histology (adenocarcinoma); prior systemic therapy history (typically gemcitabine + cisplatin ± durvalumab failed); `C78.x` / `C79.x` for metastatic sites
Advanced unresectable / metastatic HER2+ (IHC 3+) gallbladder carcinoma	`C23` (malignant neoplasm of gallbladder)	HER2 IHC 3+ pathology report; histology (adenocarcinoma typical); prior systemic therapy history; `C78.x` / `C79.x` for metastatic sites
Advanced unresectable / metastatic HER2+ (IHC 3+) extrahepatic cholangiocarcinoma	`C24.0` (extrahepatic bile duct) / `C24.1` (ampulla of Vater) / `C24.8` (overlapping) / `C24.9` (biliary tract, unspecified)	HER2 IHC 3+ pathology report; histology (adenocarcinoma typical); anatomic site documentation; prior systemic therapy history; metastatic site codes

Biliary tract cancer (BTC) primary ICD-10 codes

Code	Location
`C22.1`	Intrahepatic bile duct carcinoma (intrahepatic cholangiocarcinoma)
`C23`	Malignant neoplasm of gallbladder
`C24.0`	Extrahepatic bile duct (perihilar / Klatskin tumor, distal CBD)
`C24.1`	Ampulla of Vater
`C24.8`	Overlapping sites of biliary tract
`C24.9`	Biliary tract, unspecified

Secondary metastatic site codes (add as appropriate)

Code	Site
`C78.0x`	Secondary malignant neoplasm of lung (R/L/unspec) — common BTC met site
`C78.6`	Secondary malignant neoplasm of peritoneum and retroperitoneum — common BTC met site
`C78.7`	Secondary malignant neoplasm of liver — for extrahepatic/gallbladder primaries with hepatic mets
`C79.51`	Secondary malignant neoplasm of bone
`C77.x`	Secondary and unspecified malignant neoplasm of lymph nodes (regional/distant)

Indication-specific PA criteria are universal. Every major payer requires (1) ICD-10 confirming BTC (intrahepatic, gallbladder, or extrahepatic), (2) line-of-therapy documentation showing previously treated advanced/metastatic disease (typically gemcitabine + cisplatin ± durvalumab first-line per current NCCN), (3) HER2 IHC 3+ pathology report with antibody clone and lab accreditation. ICD-10 alone will result in denial.

Accelerated approval status: Ziihera is an accelerated approval (Nov 20, 2024) based on the HERIZON-BTC-01 trial (NCT04466891) overall response rate and duration of response. Continued approval may be contingent on confirmatory trial results (HERIZON-BTC-302). Coverage is established across major payers as of May 2026, but verify current FDA label and your payer's medical policy for any post-marketing changes.

Site of care & place of service Verified May 2026

Now that J9276 is the permanent code (effective 7/1/2025), Ziihera bills cleanly across all sites of care. The 60-minute first-dose infusion plus active reaction monitoring is typically performed in a hospital outpatient infusion center, ambulatory infusion suite, or physician oncology office equipped for chemo-class infusions. Subsequent 30-minute infusions transition cleanly to physician office or freestanding infusion suites. Major commercial payers (UnitedHealthcare, Aetna, BCBS) run site-of-care UM steering specialty oncology drugs out of HOPD for subsequent cycles — document clinical rationale if HOPD continued past Cycle 1.

Historical C9302 transitional pass-through period (4/1/2025 – 6/30/2025): During this 3-month window, Ziihera billed under C9302 was eligible for separate OPPS pass-through payment in HOPD settings only (UB-04 / 837I). Physician offices and freestanding infusion suites billing C9302 typically saw it denied or bundled because C-codes are OPPS-only. The transition to permanent J9276 on 7/1/2025 removed this constraint — J9276 bills universally. Audit any straddle claims from this period to ensure correct code by date of service.

Setting	POS	Claim form	Payer steering
Physician oncology office	11	CMS-1500 / 837P	Preferred by commercial UM (Cycle 2+)
Ambulatory infusion suite (AIC) / freestanding infusion center	49	CMS-1500 / 837P	Preferred by commercial UM
Oncology ASC	24	CMS-1500 / 837P	Acceptable
Hospital outpatient (on-campus)	22	UB-04 / 837I	Acceptable Cycle 1 (60-min first infusion); disfavored Cycle 2+ by most commercial UM
Hospital outpatient (off-campus PBD)	19	UB-04 / 837I	Disfavored after first cycle by most commercial UM
Patient home	12	CMS-1500 (with home infusion)	Rare given infusion-reaction risk + LVEF monitoring requirements; clinic-based delivery preferred

First-dose recommendation: Schedule the first Ziihera dose in a setting with infusion-reaction management capability and a 60-minute infusion window plus observation. Many practices use HOPD or AIC for Cycle 1 and transition to physician office (POS 11) for Cycle 2+ once tolerability is established. Document this clinical rationale in chart for any HOPD site-of-care UM appeal on subsequent cycles.

Claim form field mapping JazzCares Reimbursement Guide 2026

Standard Ziihera claims typically have one J9276-JZ line + one J9276-JW line (partial-vial waste from weight-based dose vs 300 mg vial). Account for 96413 admin line (96415 only if extended infusion).

Information	CMS-1500 box	Notes
NPI	17b	Rendering provider
NDC qualifier + 11-digit NDC + UoM + qty	24A shaded area	N4 + `68727-950-01` + ML + total mL drawn (e.g., 28 mL for 1400 mg administered + 2 mL discarded = 30 mL of 5-vial reconstituted solution)
HCPCS J9276 + JZ (administered units)	24D (drug line)	Units = administered mg ÷ 2 (1 unit = 2 mg); e.g., 1400 mg = 700 units
HCPCS J9276 + JW (wasted units)	24D (separate drug line)	Required when waste exists (most weight-based doses); wasted mg ÷ 2 = JW units; e.g., 100 mg wasted = 50 units
Drug units	24G	Per line; JZ units + JW units must equal (vials drawn × 300) ÷ 2
CPT 96413 (admin line)	24D (admin line)	Chemo IV, single substance, first 60 min (every Ziihera encounter; first dose and most subsequent doses)
CPT 96415 (admin line)	24D (admin line)	Only if reaction-driven infusion extends past 60 min
ICD-10	21	BTC primary (C22.1, C23, C24.x); pair with metastatic-site C78.x / C79.x codes
PA number	23	Required by all major commercial payers; HER2 IHC 3+ pathology report must accompany PA submission

Phase 3 Get paid HER2 IHC 3+ pathology report attachment to PA is non-negotiable. Archival tissue retrieval is often required for BTC patients not originally HER2-tested.

Payer policy snapshot Reviewed May 2026

All major payers require PA. Universal gate: HER2 IHC 3+ from an FDA-approved companion diagnostic. Aetna CPB 1075 and equivalent UHC/BCBS policies all hinge on the pathology report.

Payer	PA?	Documentation focus	Site-of-care UM
UnitedHealthcare Oncology Med Coverage Policy	Yes	HER2 IHC 3+ pathology report (FDA-approved companion diagnostic); ICD-10 confirming BTC; previously treated advanced/metastatic (typically gemcitabine + cisplatin ± durvalumab failed); baseline LVEF	Aggressive: site-of-care steering away from HOPD via Optum-managed program from Cycle 2 onward
Aetna CPB 1075 (Ziihera/zanidatamab-hrii)	Yes	HER2 IHC 3+ documentation by FDA-approved companion diagnostic (VENTANA PATHWAY 4B5 or equivalent); aligned with NCCN BTC compendium HER2 entry; previously treated advanced/metastatic disease; ECOG performance status	Yes (separate Site-of-Care policy; HOPD steering after Cycle 1)
BCBS plans Vary by plan	Yes	Generally aligned with NCCN BTC compendium HER2 entry + FDA label; HER2 IHC 3+ pathology report required; some plans (Anthem, BCBS-MA) require baseline LVEF documentation	Plan-specific; most have specialty-mAb site-of-care steering after first cycle
Carelon (Anthem) Medical Drug Clinical Criteria	Yes	Published Ziihera-specific policy: HER2 IHC 3+ confirmed; previously treated unresectable/metastatic BTC; appropriate prior systemic therapy lines documented	Standard site-of-care UM applies
Medicare All MACs — LCDs + NCCN compendium	No (Part B medical benefit)	All MACs cover J9276 for the FDA-approved indication with appropriate ICD-10 (C22.1/C23/C24.x) and HER2 IHC 3+ documentation; NCCN compendium support for HER2+ BTC post-progression setting	Limited; Medicare has no formal site-of-care UM

Step therapy

Ziihera is a later-line therapy by FDA label design (previously treated unresectable/metastatic BTC). Step therapy is typically baked into the line-of-therapy documentation rather than enforced as a separate gate. Expect payers to require evidence of at least one prior line of systemic therapy for metastatic BTC — typically gemcitabine + cisplatin ± durvalumab (current NCCN preferred first-line for unresectable/metastatic BTC) before approving Ziihera. Document progression on or intolerance to prior regimen.

NCCN compendium support

NCCN added zanidatamab-hrii to its Biliary Tract Cancers compendium following the November 2024 FDA approval. The recommendation is Category 2A in the post-progression molecular-targeted setting for HER2 IHC 3+ tumors (extrahepatic, gallbladder, and intrahepatic BTC). Compendium support is the practical backbone for Medicare and commercial coverage acceptance.

Medicare reimbursement CMS Q2 2026 (live)

Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.

Q2 2026 payment snapshot — J9276

Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions

ASP + 6%

$24.996

per unit (1 unit = 2 mg) · ~$12.498/mg

70 kg patient (1400 mg)

$17,497.20

700 units × ASP+6% (admin only; JW pays 50 units ≈ $1,250 additional)

90 kg patient (1800 mg)

$22,496.40

900 units × ASP+6% (exact 6-vial dose; zero waste)

Annualized cost (70 kg patient, 20 mg/kg q14d): 1 dose per cycle × ~26 cycles per year = 26 infusions; ~$487,422/year administered drug cost at Medicare ASP+6% before sequestration. With typical 50-unit JW each cycle: ~$519,917/year total drug paid before sequestration. After ~2% sequestration: ~$509,518/year actual paid. ASP is updated quarterly by CMS — next update: July 1, 2026 for Q3.

Coverage

No NCD specific to zanidatamab-hrii. Coverage falls under MAC LCDs for biologics + the generic drug-coverage framework. All MACs cover J9276 for the FDA-approved on-label indication with appropriate ICD-10 (C22.1, C23, C24.x) and HER2 IHC 3+ pathology documentation. NCCN compendium support present for HER2+ BTC.

Code history — the C9302 → J9276 transition

Nov 20, 2024 – Mar 31, 2025 — Following the November 20, 2024 FDA accelerated approval, Ziihera billed under unclassified J3490 or J9999 with NDC and dose documentation. No HCPCS-specific code yet assigned.
Apr 1, 2025 – Jun 30, 2025 — C9302 transitional pass-through code activated for OPPS billing. Hospital outpatient departments billed UB-04 / 837I with C9302 to receive separate pass-through payment. Physician offices and freestanding infusion suites typically could NOT bill C9302 (OPPS-only code); they continued using J3490 / J9999 with NDC.
J9276 effective Jul 1, 2025 — permanent code "Injection, zanidatamab-hrii, 2 mg" assigned via CMS HCPCS Quarterly Update. C9302 deactivated June 30, 2025. J9276 bills universally across all sites of care (CMS-1500 / 837P and UB-04 / 837I). For all dates of service 7/1/2025 forward, use J9276.
Q2 2026 ASP+6%: $24.996 per unit (2 mg). Verify your MAC's exact crosswalk date for any claims that straddle the transitional period.

Patient assistance — JazzCares for Ziihera Jazz Pharmaceuticals verified May 2026

JazzCares for Ziihera (Jazz Pharmaceuticals): 1-833-533-JAZZ (1-833-533-5299) / jazzcares.com — benefits investigation, prior authorization assistance, appeal support, copay program enrollment, and PAP referrals
Ziihera Copay Program (commercial copay): eligible commercially insured patients may pay reduced out-of-pocket per infusion through the manufacturer copay program; verify current annual maximum benefit and program rules at enrollment (excludes Medicare, Medicaid, federal program patients)
Jazz Patient Assistance Program (PAP): free Ziihera for uninsured / underinsured patients meeting income eligibility criteria (typically based on household income relative to Federal Poverty Level — verify current threshold at enrollment); enrollment processed through JazzCares
Foundations for Medicare patients: refer to PAN Foundation, HealthWell Foundation, CancerCare, and Good Days — verify open biliary tract cancer / cholangiocarcinoma / gallbladder cancer copay funds quarterly (oncology fund availability is highly volatile). Cholangiocarcinoma Foundation also offers patient resources.
HER2 IHC testing assistance: JazzCares can coordinate HER2 IHC 3+ testing for patients not previously tested — verify current testing assistance program details with the Access Center.
Web: ziihera.com (patient site) / ziiherahcp.com (HCP portal) / jazzpharma.com (corporate)

Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance, and OOP max? Run a CareCost Estimate — J9276 pre-loaded.

Phase 4 Fix problems Missing HER2 IHC 3+ documentation, cross-product confusion with Bizengri, unit-math errors (2 mg = 1 unit), and missing JW lines on weight-based doses are the recurring problems.

Common denials & how to fix them

Denial reason	Common cause	Fix
#1: HER2 IHC 3+ documentation missing or insufficient	PA submitted without HER2 IHC pathology report attached; or report shows IHC 2+ (not eligible regardless of ISH); or testing performed without FDA-approved companion diagnostic; or non-CAP/CLIA lab	Attach full surgical or biopsy pathology report showing HER2 IHC 3+ score, antibody clone (typically 4B5 from VENTANA PATHWAY), staining intensity and percent positive cells, lab accreditation, report date, and ordering pathologist. If BTC specimen was never HER2-tested, request retrospective IHC on archival FFPE block (1–2 week typical turnaround). IHC 2+ patients are NOT eligible — do not appeal with ISH amplification.
Wrong HCPCS code submitted	Ziihera accidentally billed under J9382 (Bizengri/zenocutuzumab) or wrong code by cross-confusion	Resubmit with J9276 for all dates of service 7/1/2025 forward (or C9302 for HOPD claims 4/1/2025–6/30/2025). Verify HCPCS matches actual product dispensed (zanidatamab-hrii = J9276); document NDC `68727-950-01` on claim line. Bizengri is J9382 — not the same drug.
Wrong unit math (mg instead of mg/2)	Biller billed 1400 units for a 1400 mg dose, treating Ziihera as 1 mg = 1 unit like Bizengri (correct: 1400 mg = 700 units)	Resubmit with correct units. J9276 is 1 unit = 2 mg, so total mg ÷ 2 = units. A 1400 mg dose = 700 units (NOT 1400). Doubled units typically trigger payment-limit denial or audit flag.
JW line missing on weight-based dose with waste	Standard JZ submitted alone when partial-vial waste actually occurred (almost always with 300 mg vial vs weight-based 20 mg/kg dose)	Add J9276-JW line for discarded mg ÷ 2 = units. Example: 70 kg = 1400 mg admin (700 JZ) + 100 mg discarded (50 JW). JZ + JW units must equal (vials drawn × 300) ÷ 2.
JZ + JW units don't reconcile to vials drawn	Math error: JZ + JW units should equal (vials × 300) ÷ 2	Recompute: total mg drawn = vials × 300; administered mg = JZ × 2; (drawn mg − admin mg) = JW × 2. For 1400 mg dose: 5 vials = 1500 drawn, 700 JZ (1400 admin) + 50 JW (100 discarded).
Wrong admin code (96365)	Therapeutic IV billed instead of chemo IV	Resubmit with 96413 (chemo IV, single substance, first 60 min). Ziihera is an antineoplastic mAb — chemo administration codes apply per AMA classification. Most encounters do NOT need 96415 (30–60 min infusions).
C9302 billed for date of service after 6/30/2025	C9302 deactivated 6/30/2025 — must use J9276 for DOS 7/1/2025 forward	Resubmit with J9276. Audit any claims submitted in the C9302 transitional period to ensure they used C9302 only for DOS 4/1/2025 – 6/30/2025 in HOPD settings.
C9302 billed in non-HOPD setting (DOS 4/1–6/30/2025)	C-codes are OPPS-only; physician office (POS 11) cannot bill C9302	Historical fix: resubmit straddle-period claims for non-HOPD with J3490 / J9999 unclassified + NDC + dose documentation. For DOS 7/1/2025 forward, use J9276 (no setting restriction).
Wrong NDC format (vial vs carton)	Vial NDC submitted instead of 11-digit carton NDC	Use carton NDC: `68727-950-01` with N4 qualifier in 24A shaded.
PA denial — sequence-of-therapy not documented	Previously treated status not documented; prior gemcitabine + cisplatin ± durvalumab regimen not in chart	Submit complete clinical history including all prior lines of systemic therapy with dates and reason for discontinuation (progression vs toxicity). For BTC, document prior gemcitabine + cisplatin ± durvalumab (NCCN preferred first-line for unresectable/metastatic BTC).
Site of care (HOPD)	HOPD administration after first cycle on commercial plan with site-of-care UM	Move to office (POS 11) or AIC (POS 49) for Cycle 2+. Submit medical necessity letter if HOPD required (e.g., active infusion-reaction history, LVEF monitoring required, hospital-coordinated care).
Confusion with Bizengri (zenocutuzumab) coverage criteria	Biller cited NRG1 fusion-positive criteria (which apply to Bizengri/J9382) instead of HER2 IHC 3+ criteria (which apply to Ziihera/J9276)	Resubmit with HER2 IHC 3+ pathology documentation. Ziihera and Bizengri are two separate drugs with totally different molecular targets and indications — review NCCN compendium entries and FDA labels for each before resubmitting.
LVEF / cardiac assessment missing	Some commercial PA reviews request baseline LVEF (echocardiogram or MUGA) given HER2-directed mechanism	Submit baseline LVEF report (within 3 months of treatment start) and institutional cardiac monitoring protocol with appeal letter. Per label, LVEF assessment is recommended at baseline and periodically during therapy.

Frequently asked questions

What is the HCPCS code for Ziihera?

Ziihera (zanidatamab-hrii) is billed under HCPCS J9276 — "Injection, zanidatamab-hrii, 2 mg" — effective July 1, 2025. The previous transitional pass-through code C9302 ("Injection, zanidatamab-hrii, 2 mg") was deactivated June 30, 2025. From the November 20, 2024 FDA accelerated approval through March 31, 2025, doses were billed under unclassified J3490 or J9999 with NDC documentation; C9302 then carried HOPD claims April 1 – June 30, 2025 before J9276 took over permanently across all sites of care. One billable unit = 2 mg (NOT 1 mg = 1 unit — different from Bizengri J9382).

Is Ziihera the same as Bizengri?

No — these are two completely different drugs approved within weeks of each other in late 2024. Ziihera (zanidatamab-hrii) is a HER2-targeted bispecific antibody from Jazz Pharmaceuticals, billed under J9276 (formerly C9302), approved November 20, 2024 for HER2-positive (IHC 3+) biliary tract cancer (BTC). Bizengri (zenocutuzumab-zbco) is a HER2/HER3 (ErbB2/ErbB3) bispecific antibody from Merus, billed under J9382, approved December 4, 2024 for NRG1 gene fusion-positive NSCLC and pancreatic adenocarcinoma. Different mechanism, different target biomarker (HER2 IHC vs NRG1 fusion), different indication, different HCPCS, different unit (2 mg vs 1 mg). Cross-confusion between these two drugs is one of the highest-risk biller errors in 2026.

What is the billing unit for J9276?

1 unit = 2 mg, per the CMS HCPCS descriptor "Injection, zanidatamab-hrii, 2 mg." Total mg administered ÷ 2 = units billed. Ziihera is dosed weight-based at 20 mg/kg q2w, so a 70 kg patient receives 1400 mg = 700 units per infusion. Each 300 mg single-dose vial = 150 units. Verify your unit math carefully — Ziihera's 2-mg unit convention is different from most newer monoclonal antibodies (which are 1 mg = 1 unit), and miscounting by a factor of 2 is a high-frequency biller error.

What HER2 IHC threshold is required for Ziihera coverage?

FDA label and all payer policies require HER2 IHC 3+ documented on a validated companion diagnostic test (typically the VENTANA PATHWAY anti-HER2/neu [4B5] assay or equivalent). HER2 IHC 2+ is NOT eligible — even with ISH amplification confirmation, Ziihera is approved only for IHC 3+ tumors per the HERIZON-BTC-01 trial enrollment criteria. The HER2 IHC 3+ pathology report is the #1 PA documentation requirement and the #1 denial driver when missing.

Is HER2 amplification (ISH) required in addition to IHC?

No — HER2 IHC 3+ alone qualifies per FDA label. ISH (FISH or DDISH) amplification testing is NOT required for Ziihera coverage when IHC is 3+. (This differs from some other HER2-directed therapies in breast and gastric cancer that allow IHC 2+/ISH-amplified eligibility.) For Ziihera, the gate is IHC 3+ binary: positive or not. ISH reflex testing is typically performed on IHC 2+ tumors but those patients are not eligible for Ziihera regardless of ISH result.

Can Ziihera be billed outside HOPD?

Yes — now that J9276 is the permanent code (effective 7/1/2025), Ziihera bills cleanly across all sites of care (POS 11 physician office, POS 49 ambulatory infusion suite, POS 22 hospital outpatient, POS 24 ASC). During the C9302 transitional pass-through period (4/1/2025 – 6/30/2025), Ziihera was required to be billed by hospital outpatient departments on UB-04 / 837I to receive separate pass-through payment under OPPS — physician offices billing C9302 typically saw it denied or bundled. Verify any straddle claims from that period are correctly coded for the date of service.

What's the difference between C-code and J-code billing?

C-codes (C9xxx) are HCPCS Level II transitional pass-through codes used in the Hospital Outpatient Prospective Payment System (OPPS) for new high-cost drugs that don't yet have permanent J-codes. They expire after 2–3 years and are specific to HOPD billing on UB-04 / 837I — physician offices using CMS-1500 / 837P cannot generally bill them. J-codes (J9xxx) are permanent HCPCS Level II codes that bill cleanly across all sites of care. The Ziihera transition: C9302 effective 4/1/2025 → J9276 effective 7/1/2025 (C9302 deactivated 6/30/2025) is a typical accelerated-approval-to-permanent-code lifecycle.

What dose of Ziihera is given and how often?

Ziihera is dosed at 20 mg/kg IV every 2 weeks (q14d), weight-based — continue until disease progression or unacceptable toxicity. The first infusion is administered over 60 minutes; if well-tolerated, subsequent infusions may be administered over 30 minutes. Reconstitute each 300 mg lyophilized single-dose vial with 6 mL Sterile Water for Injection to yield 50 mg/mL. Further dilute calculated dose in 250 mL of 0.9% Sodium Chloride Injection per label (do NOT use 5% Dextrose).

What is the Medicare reimbursement for J9276?

For Q2 2026, the Medicare Part B payment limit for J9276 is $24.996 per unit (2 mg) at ASP + 6% — equivalent to approximately $12.498 per mg. A weight-based 20 mg/kg dose for a 70 kg patient = 1400 mg = 700 units × $24.996 = $17,497.20 per dose (administered drug only). With 5 vials drawn (1500 mg) and 100 mg discarded, JW reimbursement adds another ~$1,250 = approximately $18,747 total drug payment. Cycles are every 14 days; an annualized course (~26 cycles per year) is roughly ~$487,400/year in administered drug cost (ASP + 6%) before sequestration.

Why is HER2 IHC 3+ documentation the most common denial?

Ziihera coverage is gated entirely on a HER2 IHC 3+ pathology report from an FDA-approved companion diagnostic. Biliary tract cancer (BTC) HER2 testing is not historically routine in many community pathology workflows — unlike breast/gastric cancer where HER2 IHC is reflexive. Many BTC specimens were never originally tested, requiring repeat IHC on archival tissue. PA denial typically cites: (1) no IHC result on file, (2) IHC 2+ result (does not qualify — even with ISH+), (3) IHC performed without an FDA-approved companion diagnostic assay, (4) IHC performed at a non-CAP/CLIA-certified lab. Always submit the full pathology report showing antibody clone (typically 4B5), staining intensity, percent positive cells, and lab accreditation.

Reference Sources & methodology Every claim on this page is sourced. Methodology and review history below.

Source documents

DailyMed — ZIIHERA (zanidatamab-hrii) Prescribing Information (setid ae5d9425-...)
FDA-approved label revised July 1, 2025; NDC 68727-950-01 single-vial and 68727-950-02 2-vial carton; 300 mg lyophilized single-dose vial; reconstitution (6 mL SWFI → 50 mg/mL); dilution in 250 mL 0.9% NaCl only; 60-min first dose, 30-min subsequent; BOXED warning for embryo-fetal toxicity confirmed
FDA Drugs@FDA — Ziihera BLA 761416
Approval history: accelerated approval November 20, 2024 for previously treated HER2+ (IHC 3+) biliary tract cancer based on HERIZON-BTC-01 trial (NCT04466891)
Jazz Pharmaceuticals — FDA Approval Announcement (November 20, 2024)
Official manufacturer announcement: first and only FDA-approved HER2-directed therapy for biliary tract cancer
ClinicalTrials.gov — HERIZON-BTC-01 trial (NCT04466891)
Pivotal phase IIb single-arm trial supporting Ziihera accelerated approval in HER2-positive (IHC 3+) biliary tract cancer
CMS — Medicare Part B Drug ASP Pricing File
Q2 2026 quarterly file, effective April 1 – June 30, 2026; J9276 payment limit $24.996 per 2 mg unit
CMS — HCPCS Quarterly Update
J9276 permanent code effective July 1, 2025; C9302 transitional pass-through deactivated June 30, 2025; descriptor "Injection, zanidatamab-hrii, 2 mg"; 1 unit = 2 mg
JazzCares — Ziihera Billing and Coding Guide
Manufacturer billing reference (Dec 2024 first edition; verify current version): NDC, dosing math, JZ/JW guidance, prior authorization documentation, payer policy overview
ZiiheraHCP.com — HCP Portal
Manufacturer HCP resources: dosing/admin reference (20 mg/kg q14d, 60-min first / 30-min subsequent), HER2 IHC testing brochure, treatment guide
Ziihera.com — Patient Site
Patient-facing site; copay program information and patient brochures
Jazz Pharmaceuticals — Corporate site
Manufacturer corporate site; Ziihera product information and pipeline
NCCN Clinical Practice Guidelines in Oncology — Biliary Tract Cancers (current version)
NCCN compendium support for HER2+ (IHC 3+) biliary tract cancer in the post-progression molecular-targeted setting (Category 2A)
Aetna CPB 1075 — Zanidatamab-hrii (Ziihera)
Aetna Clinical Policy Bulletin specific to Ziihera/zanidatamab-hrii; HER2 IHC 3+ documentation and previously treated status criteria
UnitedHealthcare — Oncology Medication Clinical Coverage Policy
UHC oncology medical drug coverage policy; HER2 IHC 3+ pathology report and prior systemic therapy requirements
Carelon Medical Benefit Management — Ziihera (zanidatamab-hrii) Clinical Criteria
Carelon (formerly AIM Specialty Health) clinical criteria for Ziihera coverage; covers Anthem/Elevance plans
FDA National Drug Code Directory
NDC 68727-950-01 verification for Ziihera 300 mg single-dose vial
AJMC — FDA Approves Zanidatamab-hrii for HER2+ Biliary Tract Cancer
Trade press coverage of November 20, 2024 FDA approval; HERIZON-BTC-01 trial summary
Jazz Pharmaceuticals — NCCN Compendium Update for Ziihera (Dec 2024)
Confirmation of NCCN Biliary Tract Cancers compendium inclusion for zanidatamab-hrii post-FDA approval

About this page

We maintain this page as a living reference. Medicare ASP pricing is bound to our underlying CareCost data layer and refreshes automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.

Found an error? Email hello@carecostestimate.com.

Refresh cadence

Element	Cadence	How it's refreshed
Medicare ASP pricing	Quarterly	Auto-bound to CareCost ASP layer; updates on CMS file release.
Payer policies (UHC, Aetna CPB 1075, BCBS, Carelon)	Semi-annual	Manual review against published payer policy documents.
HCPCS / CPT / modifier rules	Annual	Reviewed against CMS HCPCS quarterly files and AMA CPT releases.
NDC, dosing, FDA label, indication	Event-driven	Tied to manufacturer document version + FDA label revision date. Accelerated approval (Nov 2024) under active monitoring for confirmatory data (HERIZON-BTC-302).

Reviewer

SME-audited 2026-05-22 — corrections applied. This page was audited 2026-05-22 against DailyMed setid ae5d9425-fae5-4541-a158-150998343348 (Jazz Pharmaceuticals label, revised July 1, 2025). Corrections applied: (1) Embryo-fetal toxicity reclassified as BOXED warning (was listed under Key warnings); (2) Label revision date updated from "Nov 2024 accelerated approval" to "July 1, 2025"; (3) NDC corrected to include 2-vial carton 68727-950-02 alongside single-vial 68727-950-01; (4) Dose-modification option (15 mg/kg q14d reduction) added per label; (5) Incidence rates added for infusion reactions (31%), diarrhea (48%), LVEF decline (4.3%). Re-verify each cited source for high-stakes claims.

Change log

May 22, 2026 — SME audit. (1) Embryo-fetal toxicity confirmed as BOXED warning per DailyMed (was previously listed only under Key warnings); page updated. (2) Label revision date updated from Nov 2024 to July 1, 2025 per DailyMed setid ae5d9425-fae5-4541-a158-150998343348. (3) NDC expanded to include 2-vial carton 68727-950-02 alongside single-vial 68727-950-01. (4) Added label-permitted 15 mg/kg dose-reduction option for adverse reactions. (5) Added incidence rates: infusion reactions 31%, diarrhea 48%, LVEF decline 4.3%.
May 21, 2026 — Initial publication. ASP data: Q2 2026 ($24.996 per 2 mg unit). Manufacturer source: JazzCares 2024/2026 billing guide. FDA label: November 2024 accelerated approval (BLA 761361 / 761416). Indication: previously treated unresectable/metastatic HER2+ (IHC 3+) biliary tract cancer. HCPCS history: J3490 (Nov 2024 – Mar 2025), C9302 (Apr – Jun 2025, OPPS only), J9276 permanent (Jul 2025 forward).

Methodology

Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. Indication list is verified against the current FDA label revision. We do not paraphrase from billing-software vendor blogs.

Ziihera (zanidatamab-hrii) — HCPCS J9276

Instant Answer — the 5 things you need to bill J9276

Dosing & unit math FDA label verified May 2026

Adult dosing

Preparation

Premedication for infusion-related reactions

Worked example — 70 kg patient, standard 20 mg/kg dose

NDC reference FDA NDC Directory verified May 2026

HER2 IHC 3+ testing — the universal coverage gate NCCN / payer policies verified May 2026

FDA-approved companion diagnostic

HER2 IHC scoring (BTC-specific criteria)

HER2 ISH (FISH/DDISH) — NOT required

Administration codes CPT verified May 2026

Modifiers CMS verified May 2026

JW + JZ — both lines on most Ziihera claims

Worked example — 70 kg patient (1400 mg dose)

Worked example — 90 kg patient (1800 mg dose, zero waste)

Modifier 25 — same-day E/M

340B modifiers (JG, TB)

ICD-10-CM by indication FY2026 verified May 2026

Biliary tract cancer (BTC) primary ICD-10 codes

Secondary metastatic site codes (add as appropriate)

Site of care & place of service Verified May 2026

Claim form field mapping JazzCares Reimbursement Guide 2026

Payer policy snapshot Reviewed May 2026

Step therapy

NCCN compendium support

Medicare reimbursement CMS Q2 2026 (live)

Q2 2026 payment snapshot — J9276

Coverage

Code history — the C9302 → J9276 transition

Patient assistance — JazzCares for Ziihera Jazz Pharmaceuticals verified May 2026

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Ziihera?

Is Ziihera the same as Bizengri?

What is the billing unit for J9276?

What HER2 IHC threshold is required for Ziihera coverage?

Is HER2 amplification (ISH) required in addition to IHC?

Can Ziihera be billed outside HOPD?

What's the difference between C-code and J-code billing?

What dose of Ziihera is given and how often?

What is the Medicare reimbursement for J9276?

Why is HER2 IHC 3+ documentation the most common denial?

Source documents

About this page

Refresh cadence

Reviewer

Change log

Methodology

Stop calculating Ziihera copays by hand.