Jazz Pharmaceuticals has received the European Commission (EC) conditional marketing authorisation for Ziihera (zanidatamab) to treat a type of biliary tract cancer (BTC).
Ziihera is a dual HER2-targeted bispecific antibody that works by binding to extracellular domains 2 and 4 on separate HER2 monomers.
The drug inhibits tumour growth through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.
Ziihera is indicated as a monotherapy for adults with unresectable locally advanced or metastatic HER2-positive BTC who have undergone at least one prior systemic therapy.
The recommended dose for Ziihera is 20mg/kg, administered intravenously every two weeks until disease progression or unacceptable toxicity.
According to Jazz, Ziihera is the first HER2-targeted therapy to receive conditional authorisation for HER2-positive BTC in the European Union (EU).
The EC decision applies to all EU Member States, Iceland, Liechtenstein, and Norway.
Continued approval is contingent upon results from the ongoing Phase 3 HERIZON-BTC-302 trial, which compares zanidatamab combined with standard care to standard care alone.
Jazz Pharmaceuticals executive vice president, research and development global head, and chief medical officer Robert Iannone said: “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 authorised 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 tumours.”
The EC authorisation was based on data from the Phase 2b HERIZON-BTC-01 trial in 87 patients, with 80 having centrally confirmed HER2-positive tumours.
The clinical trial met its primary endpoint, showing a confirmed objective response rate of 41.3% at a median follow-up of 21.9 months, including two complete responses.
In a subgroup with IHC 3+ tumours, Ziihera showed a confirmed objective response rate of 51.6%, with a median duration of response of 14.9 months and a median overall survival of 18.1 months.
The safety profile was assessed in 87 patients, with common adverse reactions including diarrhoea, infusion-related reactions, abdominal pain, anaemia, and fatigue.
Serious adverse reactions occurred in 16.1% of patients, with diarrhoea, fatigue, and increased alanine aminotransferase being the most frequent.
Hannover Medical School Department of Gastroenterology, Hepatology and Endocrinology managing senior consultant and professor Arndt Vogel said: “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.”
