Ziihera (zanidatamab)
An approved treatment for Cholangiocarcinoma.
The same compound appears under different names depending on the context. Here is how to identify Zanidatamab wherever you encounter it, plus the key facts at a glance.
- Generic name
- Zanidatamab
- Brand name
- Ziihera
- Development codes
- ZW25, zanidatamab-hrii
- Drug class
- Bispecific monoclonal antibody (HER2-targeted)
- Manufacturer
- Jazz Pharmaceuticals
- How it's taken
- Zanidatamab is given as an intravenous infusion of 20 mg/kg once every 2 weeks in a clinic or infusion center.
An intravenous antibody for previously treated HER2-positive biliary tract cancer, including bile duct cancer and gallbladder cancer. It grips two different spots on the HER2 protein at once, and it is given without chemotherapy.
Where Zanidatamab fits
Approved for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. It sits in the second-line-and-beyond setting after gemcitabine-based chemotherapy, and is the chemotherapy-free option for patients whose tumors are strongly HER2-positive. It is distinct from the FGFR-targeted drugs pemigatinib and futibatinib, which serve a different molecular subgroup (FGFR2 fusions), so molecular profiling of the tumor determines which of these paths is open.
How Zanidatamab works
HER2 is a growth-signaling protein that sits on the surface of some cancer cells and tells them to keep dividing. Ordinary HER2 antibodies attach to one spot on the protein. Zanidatamab is bispecific, meaning it grabs two separate places on HER2 at the same time. That double grip clusters the receptors together and pulls them inside the cell, so fewer HER2 receptors remain on the surface to receive growth signals. It also flags the cancer cell for destruction by the immune system through several mechanisms, including complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity and phagocytosis.
Mechanism: Bispecific HER2-directed antibody binding two separate sites on HER2
Side effects and safety
Zanidatamab carries a Boxed Warning for severe diarrhea and for embryo-fetal toxicity. Severe, life-threatening, and fatal diarrhea has occurred when it is given with chemotherapy for stomach or esophageal cancer, and the label says to start anti-diarrhea medicine (loperamide) at the first loose stool even when it is given alone. Exposure during pregnancy can harm the fetus, so pregnancy status is verified before starting and effective contraception is needed during treatment and for 4 months after the last dose. Among 80 patients with HER2-positive biliary tract cancer, the most common side effects were diarrhea (50%), infusion-related reactions (35%), abdominal pain (29%), and fatigue (24%). Serious side effects occurred in 54% of patients, most often biliary obstruction (15%), biliary tract infection (8%), and sepsis (8%). The drug can reduce the heart's pumping strength (left ventricular ejection fraction), so heart function is checked before treatment and at intervals during it. Diarrhea can be severe and should be reported promptly rather than managed alone.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Zanidatamab
Zanidatamab is given as an intravenous infusion of 20 mg/kg once every 2 weeks in a clinic or infusion center. Premedication is given before each dose to reduce the risk of infusion-related reactions, which happen most often on the first day of dosing and usually resolve within a day. Treatment continues until the cancer progresses or side effects become unacceptable. No chemotherapy is given alongside it in the biliary tract cancer indication.
Availability and cost
Only available as the brand-name product.
An engineered bispecific antibody for a molecularly defined subset of an already rare cancer. Roughly 12,000 people across the U.S., Europe, and Japan are diagnosed with HER2-positive biliary tract cancer each year, and that small eligible population combined with complex biologic manufacturing drives orphan biologic pricing.
Help paying for Ziihera
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Copay help
Eligible commercially insured patients may pay as little as $0 per prescription, subject to an annual maximum.
For: private insurance · source - Free medicine program
Uninsured or underinsured patients who meet financial criteria may get ZIIHERA at no cost.
For: no insurance, underinsured · source - Insurance and case manager help
Help with benefits investigations, prior authorizations and appeals, and referrals to other financial assistance.
The official page does not say who qualifies. Ask the program. · source
Good to know: The patient page says copay may be as little as $0; the HCP page (BTC) says as little as $10. Confirm the current amount with JazzCares. Phone 1-833-533-JAZZ, Mon-Fri 8 AM-8 PM ET.
- From a charity · The Assistance FundBiliary Tract Cancer fundWaitlist
Pays for: Copays, coinsurance, deductibles and other health-related expenses.
The foundation says: “WAITLIST — Accepting Waitlist Patients. TAF is currently accepting requests to join the enrollment waitlist for this program. Waitlists a…”
Access and eligibility
Tumor tissue must test HER2-positive at the IHC 3+ level using an FDA-approved test before zanidatamab can be prescribed for biliary tract cancer. The approved indication covers adults with unresectable or metastatic disease who have already received prior therapy. Patients whose baseline heart ejection fraction is below 50% were not studied, and safety in that group is not established.
Access program details are provided for informational purposes and may vary based on insurance coverage, geographic location, and individual circumstances. Confirm current eligibility directly with the manufacturer or your specialty pharmacy.
Clinical trial results
Approval rested on Cohort 1 of the Phase 2b HERIZON-BTC-01 trial, the largest trial to date in this population, which enrolled 87 patients and evaluated 62 with HER2 IHC 3+ biliary tract cancer who had already received gemcitabine-based therapy. The objective response rate was 52% by independent central review, with a median duration of response of 14.9 months. The Phase 3 confirmatory trial HERIZON-BTC-302 (NCT06282575) is ongoing in the first-line setting; continued approval for this indication may depend on its results. Separately, on August 25, 2026, the FDA approved zanidatamab combinations for first-line HER2-positive gastroesophageal adenocarcinoma based on the Phase 3 HERIZON-GEA-01 trial, where zanidatamab plus tislelizumab and chemotherapy lowered the risk of cancer growth or death by 37% and the risk of death by 28% compared with trastuzumab plus chemotherapy.
Development history
Zanidatamab (ZW25) was first developed by Zymeworks, which engineered the bispecific format, and is now developed by Jazz Pharmaceuticals and BeiGene under license from Zymeworks. The FDA granted Breakthrough Therapy designation in previously treated HER2 gene-amplified biliary tract cancer, two Fast Track designations, and Orphan Drug designation for both biliary tract cancer and gastroesophageal adenocarcinoma. Accelerated approval for biliary tract cancer came on November 20, 2024, making it the first and only dual HER2-targeted bispecific antibody approved for this cancer in the U.S. A first-line gastroesophageal adenocarcinoma approval followed in August 2026.
Explore Cholangiocarcinoma trials
Other Cholangiocarcinoma treatments
Biliary tract cancer is increasingly split by molecular subtype rather than treated as one disease. Patients with FGFR2 fusions or rearrangements may be candidates for pemigatinib or futibatinib, oral FGFR inhibitors. Patients with IDH1 mutations may be candidates for ivosidenib. Zanidatamab addresses a separate group, those whose tumors strongly overexpress HER2. Comprehensive genomic profiling of the tumor is what determines which of these targeted options, if any, applies, and it is worth requesting early rather than after several lines of chemotherapy.
Common questions about Zanidatamab
▸What is Zanidatamab (Ziihera)?
An intravenous antibody for previously treated HER2-positive biliary tract cancer, including bile duct cancer and gallbladder cancer. It grips two different spots on the HER2 protein at once, and it is given without chemotherapy.
▸How does Zanidatamab work?
HER2 is a growth-signaling protein that sits on the surface of some cancer cells and tells them to keep dividing. Ordinary HER2 antibodies attach to one spot on the protein. Zanidatamab is bispecific, meaning it grabs two separate places on HER2 at the same time. That double grip clusters the receptors together and pulls them inside the cell, so fewer HER2 receptors remain on the surface to receive growth signals. It also flags the cancer cell for destruction by the immune system through several mechanisms, including complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity and phagocytosis.
▸What are the side effects of Zanidatamab?
Zanidatamab carries a Boxed Warning for severe diarrhea and for embryo-fetal toxicity. Severe, life-threatening, and fatal diarrhea has occurred when it is given with chemotherapy for stomach or esophageal cancer, and the label says to start anti-diarrhea medicine (loperamide) at the first loose stool even when it is given alone. Exposure during pregnancy can harm the fetus, so pregnancy status is verified before starting and effective contraception is needed during treatment and for 4 months after the last dose. Among 80 patients with HER2-positive biliary tract cancer, the most common side effects were diarrhea (50%), infusion-related reactions (35%), abdominal pain (29%), and fatigue (24%). Serious side effects occurred in 54% of patients, most often biliary obstruction (15%), biliary tract infection (8%), and sepsis (8%). The drug can reduce the heart's pumping strength (left ventricular ejection fraction), so heart function is checked before treatment and at intervals during it. Diarrhea can be severe and should be reported promptly rather than managed alone.
▸How is Zanidatamab taken?
Zanidatamab is given as an intravenous infusion of 20 mg/kg once every 2 weeks in a clinic or infusion center. Premedication is given before each dose to reduce the risk of infusion-related reactions, which happen most often on the first day of dosing and usually resolve within a day. Treatment continues until the cancer progresses or side effects become unacceptable. No chemotherapy is given alongside it in the biliary tract cancer indication.
▸Is Zanidatamab FDA approved?
Yes, Zanidatamab (Ziihera) is FDA approved (2024) for the treatment of Cholangiocarcinoma.
▸What does "bispecific" mean for zanidatamab?
Most antibodies attach to one spot on their target. Zanidatamab attaches to two different places on the HER2 protein at the same time. That double grip clusters HER2 receptors and pulls them inside the cancer cell, removing them from the surface where they would otherwise receive growth signals.
▸Do I need HER2 testing before taking zanidatamab?
Yes. Tumor tissue must test HER2-positive at the IHC 3+ level using an FDA-approved test. Only a subset of biliary tract cancers meet that threshold, so genomic and protein profiling of the tumor is required before the drug can be prescribed.
▸Is zanidatamab given with chemotherapy?
Not for biliary tract cancer. It is given on its own as an intravenous infusion every 2 weeks, which is why it is described as a chemotherapy-free option. In the separate 2026 approval for first-line gastroesophageal adenocarcinoma, it is given with chemotherapy and, in one of the two approved regimens, with tislelizumab.
▸How well did it work in trials?
In Cohort 1 of the HERIZON-BTC-01 trial, 52% of patients with HER2 IHC 3+ biliary tract cancer had their tumors shrink meaningfully, and the median length of that response was 14.9 months. This was an accelerated approval, so a Phase 3 confirmatory trial is ongoing.
▸What is the Boxed Warning?
Zanidatamab carries a Boxed Warning for severe diarrhea and for embryo-fetal toxicity. Severe and sometimes fatal diarrhea has occurred, mainly when it is given with chemotherapy, so report loose stools right away. Exposure during pregnancy can cause serious fetal harm. Pregnancy status is verified before starting, and effective contraception is needed during treatment and for 4 months after the final dose.
▸How is it different from the FGFR inhibitors used in bile duct cancer?
Pemigatinib and futibatinib are oral pills targeting FGFR2 fusions or rearrangements. Zanidatamab is an infused antibody targeting HER2 overexpression. They serve different molecular subgroups of biliary tract cancer, so which one applies depends on what the tumor's genomic profiling shows.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Jazz Pharmaceuticals plc · 2024-11-20. Jazz Pharmaceuticals Announces U.S. FDA Approval of Ziihera (zanidatamab-hrii) for the Treatment of Adults with Previously Treated, Unresectable or Metastatic HER2-positive (IHC 3+) Biliary Tract Cancer (BTC). https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-ziiherar/
- Jazz Pharmaceuticals, Inc.. ZIIHERA (zanidatamab-hrii) for injection, for intravenous use — Full Prescribing Information. https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf
- U.S. Food and Drug Administration · 2026-08-25. FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanidatamab-hrii-and-tislelizumab-jsgr-her2-positive-gastric-gastroesophageal-junction