Jazz Pharmaceuticals Secures Conditional EU Approval for Ziihera® (zanidatamab) to Treat Advanced HER2-Positive Biliary Tract Cancer
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) has announced that the European Commission (EC) has granted conditional marketing authorization for Ziihera® (zanidatamab), a dual HER2-targeted bispecific antibody, for use as a monotherapy in adults with unresectable, locally advanced or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC) who have received at least one prior systemic therapy.
This marks a pivotal moment for the treatment of a rare and aggressive group of cancers—including gallbladder cancer (GBC) and cholangiocarcinoma (CCA)—which are often diagnosed at an advanced stage when curative surgical options are no longer feasible. With approximately 26% of BTC cases globally exhibiting HER2 positivity—a biomarker linked to worse clinical outcomes—Ziihera becomes the first HER2-targeted treatment approved in the European Union (EU) specifically for this subset of BTC patients.
A Groundbreaking Step in HER2-Targeted Therapy for BTC
The EC’s decision was primarily driven by results from the Phase 2b HERIZON-BTC-01 trial, the largest of its kind in this population. The trial evaluated Ziihera as a monotherapy in 87 previously treated patients with HER2-positive BTC. The primary cohort included 80 patients with centrally confirmed HER2-positive tumors (IHC 2+/ISH+ or IHC 3+/ISH+).
Ziihera demonstrated a confirmed objective response rate (cORR) of 41.3%, including two complete responses, with a median duration of response (DOR) of 14.9 months and a median overall survival (OS) of 15.5 months. In a pre-specified subgroup of 62 patients with IHC 3+ tumors, the cORR increased to 51.6%, and the OS extended to 18.1 months.
These data highlight the clinical potential of zanidatamab to offer a durable and meaningful response in a setting where options have historically been limited. Continued authorization of Ziihera for this indication will depend on positive outcomes from the ongoing Phase 3 HERIZON-BTC-302 trial, which is evaluating the drug in combination with standard-of-care therapy in the first-line setting.
Expert and Patient Advocacy Support
“Patients with HER2-positive BTC who progress beyond first-line therapy face a grim prognosis,” said Dr. Arndt Vogel, professor of gastroenterology at Hannover Medical School. “Ziihera offers a targeted monotherapy with a favorable safety profile and compelling efficacy, representing a crucial advance in the fight against this challenging disease.”
Zorana Maravic, CEO of Digestive Cancers Europe (DiCE), added, “BTC is increasingly affecting younger patients and carries a profound personal and societal burden. The approval of Ziihera offers a beacon of hope for patients who urgently need alternatives beyond chemotherapy.”
Safety and Dosing Profile
The recommended dose of Ziihera is 20 mg/kg via intravenous infusion every two weeks, continued until disease progression or the emergence of unacceptable toxicity. Safety analysis from the HERIZON-BTC-01 study revealed that the most common adverse reactions included:
- Diarrhea (46%)
- Infusion-related reactions (33.3%)
- Abdominal pain (26.4%)
- Anemia (25.3%)
- Fatigue (24.1%)
Serious adverse events were reported in 16.1% of patients, with the most frequent being diarrhea, fatigue, and elevated liver enzymes.
Regulatory Milestones and Global Development
Ziihera’s conditional approval in the EU follows a series of significant regulatory milestones globally:
- November 2024: The U.S. Food and Drug Administration (FDA) granted accelerated approval for Ziihera for previously treated HER2-positive BTC.
- May 2025: China’s National Medical Products Administration (NMPA) issued conditional approval for the same indication.
Further approval in these regions also depends on the confirmatory Phase 3 HERIZON-BTC-302 trial.
Ziihera is being jointly developed by Jazz Pharmaceuticals and BeOne Medicines Ltd. (formerly BeiGene, Ltd.) under license from Zymeworks Inc., the original developer. Jazz holds commercialization rights in the U.S., EU, Japan, and most global markets outside of the Asia-Pacific region (excluding Japan), which remain under BeiGene’s purview.
In the U.S., Ziihera has received multiple regulatory designations, including:
- Breakthrough Therapy designation for previously treated HER2-amplified BTC
- Two Fast Track designations (as monotherapy for refractory BTC and in combination therapy for first-line gastroesophageal adenocarcinoma)
- Orphan Drug designations for BTC and GEA from both the FDA and the European Medicines Agency (EMA)
About Ziihera (zanidatamab)
Ziihera is a bispecific antibody designed to bind to two different regions (domains 2 and 4) on the HER2 receptor. This binding promotes internalization and degradation of HER2 receptors on the cancer cell surface. Ziihera also activates multiple immune mechanisms—CDC (complement-dependent cytotoxicity), ADCC (antibody-dependent cellular cytotoxicity), and ADCP (antibody-dependent cellular phagocytosis)—to promote tumor cell death.
It is under investigation across multiple clinical trials targeting HER2-expressing solid tumors beyond BTC, including gastric, breast, and gastroesophageal cancers.
About Biliary Tract Cancer
BTC represents a rare yet aggressive form of cancer comprising gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma. Though they account for fewer than 1% of all human cancers, BTCs—especially cholangiocarcinoma—are the second most common liver cancer globally. Late-stage diagnoses are common due to vague initial symptoms, and available treatments have limited durability in effectiveness.
HER2 positivity characterizes a distinct and more aggressive subtype of BTC, impacting around 12,000 patients annually across the U.S., EU, and Japan. This underscores the critical need for targeted therapies like Ziihera to address gaps in treatment following first-line therapy.
