Jazz’s Ziihera Becomes First HER2 Therapy Approved In EU For Advanced Biliary Tract Cancer

Jazz Pharmaceuticals has announced that the European Commission (EC) has granted conditional marketing authorization for Ziihera® (zanidatamab), a novel HER2-targeted bispecific antibody, as a monotherapy for adults with unresectable, locally advanced or metastatic HER2-positive biliary tract cancer (BTC) who have previously received systemic therapy. This approval makes Ziihera the first HER2-targeted therapy authorized for this rare and aggressive cancer type in the European Union, addressing a critical unmet need.

"People with HER2-positive biliary tract cancer who progress after first-line therapy face a challenging prognosis, with limited treatment options, poor tolerability, and median overall survival of only six to nine months. Zanidatamab provides a much-needed targeted monotherapy for this population, and in the HERIZON-BTC-01 trial, it demonstrated clinically meaningful and durable responses with a manageable safety profile. These data represent a welcome advance for patients with historically poor outcomes and highlight the importance of HER2 testing in biliary tract cancer to ensure eligible patients are identified for biomarker-driven treatment," said Arndt Vogel, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany. 

The EC's decision is based on data from the Phase 2b HERIZON-BTC-01 trial, the largest study of its kind in HER2-positive BTC. The trial reported a confirmed objective response rate (cORR) of 41.3% in the overall cohort and 51.6% in a subgroup of patients with IHC 3+ tumors. Median duration of response reached nearly 15 months, with a median overall survival of 18.1 months in the IHC 3+ subgroup. Continued approval is contingent on data from the ongoing Phase 3 HERIZON-BTC-302 study.

"This conditional approval represents significant progress for the patients we serve who have been diagnosed with advanced HER2-positive BTC. Ziihera is the first HER2-targeted therapy authorized in the European Union specifically for this population, and the European Commission's decision reflects both the strength of the HERIZON-BTC-01 data and the urgency for innovation in rare gastrointestinal cancers. This milestone reinforces our commitment to advancing biomarker-driven therapies that address serious unmet needs and improve patient outcomes. We are actively recruiting for our global Phase 3 trial in first-line HER2-positive BTC and continue to explore zanidatamab's potential in other HER2-expressing tumors," said Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. 

Ziihera will be administered as a 20 mg/kg intravenous infusion every two weeks, continuing until disease progression or intolerable side effects. The treatment was generally well tolerated, with the most frequent adverse events being diarrhea, infusion reactions, abdominal pain, anemia, and fatigue. The conditional authorization applies across the EU, including Iceland, Norway, and Liechtenstein.

"Biliary tract cancers are becoming more common worldwide and are increasingly affecting people under the age of 60, resulting in a significant social and economic burden. These cancers are typically diagnosed late, when patients have limited treatment options available and, unfortunately, their disease often progresses. Ziihera provides a much-needed alternative to chemotherapy for patients with HER2-positive BTC at this stage. It also brings hope to the digestive cancer patient community as another step in expanding the availability of targeted therapies," said Zorana Maravic, chief executive officer at Digestive Cancers Europe (DiCE).