Jazz Pharmaceuticals Receives European Commission Marketing Authorization for Ziihera庐 (zanidatamab) for the Treatment of Advanced HER2-Positive Biliary Tract Cancer
Jazz Pharmaceuticals (Nasdaq: JAZZ) has received conditional marketing authorization from the European Commission for Ziihera庐 (zanidatamab) for treating adults with unresectable locally advanced or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC) who have received at least one prior line of systemic therapy.
The approval is based on the Phase 2b HERIZON-BTC-01 trial results, which demonstrated significant efficacy in the largest study conducted to date in this population. Key findings include:
- Confirmed objective response rate (cORR) of 41.3% in the overall population
- Higher cORR of 51.6% in IHC 3+ tumor patients
- Median duration of response of 14.9 months
- Median overall survival of 18.1 months in IHC 3+ patients
Ziihera becomes the first HER2-targeted therapy authorized for HER2-positive BTC in the European Union. The approval extends to all EU Member States, Iceland, Norway, and Liechtenstein. Continued approval is contingent upon verification of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 trial.
Jazz Pharmaceuticals (Nasdaq: JAZZ) ha ottenuto l'autorizzazione condizionata alla commercializzazione dalla Commissione Europea per Ziihera庐 (zanidatamab), destinato al trattamento di adulti con tumore delle vie biliari (BTC) HER2-positivo (IHC 3+) localmente avanzato non resecabile o metastatico, che hanno gi脿 ricevuto almeno una linea di terapia sistemica.
L'approvazione si basa sui risultati dello studio di Fase 2b HERIZON-BTC-01, che ha dimostrato un'efficacia significativa nel pi霉 ampio studio finora condotto in questa popolazione. I principali risultati includono:
- Un tasso di risposta obiettiva confermata (cORR) del 41,3% nella popolazione complessiva
- Un cORR pi霉 elevato del 51,6% nei pazienti con tumori IHC 3+
- Durata mediana della risposta di 14,9 mesi
- Sopravvivenza globale mediana di 18,1 mesi nei pazienti IHC 3+
Ziihera diventa la prima terapia mirata contro HER2 autorizzata per il BTC HER2-positivo nell'Unione Europea. L'autorizzazione si estende a tutti gli Stati membri UE, Islanda, Norvegia e Liechtenstein. Il mantenimento dell'autorizzazione dipender脿 dalla conferma del beneficio clinico nello studio di Fase 3 HERIZON-BTC-302 in corso.
Jazz Pharmaceuticals (Nasdaq: JAZZ) ha recibido la autorizaci贸n condicional de comercializaci贸n por parte de la Comisi贸n Europea para Ziihera庐 (zanidatamab), destinado al tratamiento de adultos con c谩ncer de v铆as biliares (BTC) HER2-positivo (IHC 3+) localmente avanzado no resecable o metast谩sico, que hayan recibido al menos una l铆nea previa de terapia sist茅mica.
La aprobaci贸n se basa en los resultados del ensayo de Fase 2b HERIZON-BTC-01, que demostr贸 una eficacia significativa en el estudio m谩s grande realizado hasta la fecha en esta poblaci贸n. Los hallazgos clave incluyen:
- Tasa de respuesta objetiva confirmada (cORR) del 41,3% en la poblaci贸n general
- Una cORR m谩s alta del 51,6% en pacientes con tumores IHC 3+
- Duraci贸n media de la respuesta de 14,9 meses
- Supervivencia global media de 18,1 meses en pacientes IHC 3+
Ziihera se convierte en la primera terapia dirigida contra HER2 autorizada para BTC HER2-positivo en la Uni贸n Europea. La aprobaci贸n se extiende a todos los Estados miembros de la UE, Islandia, Noruega y Liechtenstein. La aprobaci贸n continua depender谩 de la verificaci贸n del beneficio cl铆nico en el ensayo en curso de Fase 3 HERIZON-BTC-302.
Jazz Pharmaceuticals (雮橃姢雼�: JAZZ)電� 鞝堨牅臧� 攵堦皜電ロ暅 甑唽 歆勴枆靹� 霕愲姅 鞝勳澊靹� HER2 鞏戩劚(IHC 3+) 雼措弰鞎�(BTC) 靹膘澑 頇橃瀽 欷� 斓滌唽 頃� 彀 鞚挫儊鞚� 鞝勳嫚 旃橂毳� 氚涭潃 頇橃瀽 旃橂毳� 鞙勴暣 Ziihera庐(鞛愲媹雼ろ儉毵�)鞐� 雽�頃� 鞙犽熃鞐绊暕 歆戫枆鞙勳洂須岆攵�韯� 臁瓣贝攵� 韺愲Г 項堦皜毳� 氚涭晿鞀惦媹雼�.
鞚措矆 鞀轨澑鞚� HERIZON-BTC-01 2b靸� 鞛勳儊鞁滍棙 瓴瓣臣毳� 氚旐儠鞙茧 頃橂┌, 頃措嫻 鞚戈惮歆戨嫧鞐愳劀 歆�旮堦箤歆� 歆勴枆霅� 臧�鞛� 韥� 鞐瓣惮鞐愳劀 鞙犾潣氙疙暅 須姤鞚� 鞛呾頄堨姷雼堧嫟. 欤检殧 瓴瓣臣電� 雼れ潓瓿� 臧欖姷雼堧嫟:
- 鞝勳泊 雽�靸侅瀽鞐愳劀 頇曥澑霅� 臧濌磤鞝� 氚橃潙毳�(cORR) 41.3%
- IHC 3+ 膦呾枒 頇橃瀽鞐愳劀 雿� 雴掛潃 cORR 51.6%
- 氚橃潙 歆�靻� 欷戩暀臧� 14.9臧滌洈
- IHC 3+ 頇橃瀽鞐愳劀 鞝勳泊 靸濎〈 旮瓣皠 欷戩暀臧� 18.1臧滌洈
Ziihera電� 鞙犽熃鞐绊暕 雮� HER2 鞏戩劚 BTC鞐� 雽�頃� 項堦皜霅� 斓滌磮鞚� HER2 響滌爜 旃橂鞝滉皜 霅橃棃鞀惦媹雼�. 鞚� 鞀轨澑鞚� 氇摖 EU 須岇洂甑臣 鞎勳澊鞀瀫霌�, 雲鸽ゴ鞗澊, 毽瀳韰愳妶韮�鞚胳棎 鞝侅毄霅╇媹雼�. 歆�靻嶌爜鞚� 鞀轨澑鞚� 歆勴枆 欷戩澑 3靸� HERIZON-BTC-302 鞛勳儊鞁滍棙鞐愳劀 鞛勳儊鞝� 鞚挫爯鞚� 頇曥澑霅橃柎鞎� 頃╇媹雼�.
Jazz Pharmaceuticals (Nasdaq : JAZZ) a obtenu une autorisation de mise sur le march茅 conditionnelle de la Commission europ茅enne pour Ziihera庐 (zanidatamab), destin茅 au traitement des adultes atteints d'un cancer des voies biliaires (BTC) HER2-positif (IHC 3+) localement avanc茅 non r茅s茅cable ou m茅tastatique, ayant re莽u au moins une ligne pr茅alable de traitement syst茅mique.
Cette approbation repose sur les r茅sultats de l'essai de phase 2b HERIZON-BTC-01, qui a d茅montr茅 une efficacit茅 significative dans la plus grande 茅tude r茅alis茅e 脿 ce jour sur cette population. Les r茅sultats cl茅s comprennent :
- Taux de r茅ponse objective confirm茅e (cORR) de 41,3 % dans la population globale
- cORR plus 茅lev茅 de 51,6 % chez les patients avec tumeurs IHC 3+
- Dur茅e m茅diane de la r茅ponse de 14,9 mois
- Survie globale m茅diane de 18,1 mois chez les patients IHC 3+
Ziihera devient la premi猫re th茅rapie ciblant HER2 autoris茅e pour le BTC HER2-positif dans l'Union europ茅enne. L'autorisation s'茅tend 脿 tous les 脡tats membres de l'UE, ainsi qu'脿 l'Islande, la Norv猫ge et le Liechtenstein. Le maintien de cette autorisation d茅pendra de la confirmation du b茅n茅fice clinique dans l'essai de phase 3 HERIZON-BTC-302 en cours.
Jazz Pharmaceuticals (Nasdaq: JAZZ) hat von der Europ盲ischen Kommission eine bedingte Marktzulassung f眉r Ziihera庐 (Zanidatamab) zur Behandlung von Erwachsenen mit nicht resezierbarem lokal fortgeschrittenem oder metastasiertem HER2-positivem (IHC 3+) Gallengangskarzinom (BTC) erhalten, die mindestens eine vorherige systemische Therapie erhalten haben.
Die Zulassung basiert auf den Ergebnissen der Phase-2b-Studie HERIZON-BTC-01, die eine signifikante Wirksamkeit in der bisher gr枚脽ten Studie dieser Patientengruppe zeigte. Wichtige Ergebnisse sind:
- Best盲tigte objektive Ansprechrate (cORR) von 41,3 % in der Gesamtpopulation
- H枚here cORR von 51,6 % bei Patienten mit IHC 3+ Tumoren
- Medianes Ansprechdauer von 14,9 Monaten
- Medianes Gesamt眉berleben von 18,1 Monaten bei IHC 3+ Patienten
Ziihera ist die erste HER2-targeted Therapie, die f眉r HER2-positives BTC in der Europ盲ischen Union zugelassen wurde. Die Zulassung gilt f眉r alle EU-Mitgliedstaaten sowie Island, Norwegen und Liechtenstein. Die fortlaufende Zulassung h盲ngt von der Best盲tigung des klinischen Nutzens in der laufenden Phase-3-Studie HERIZON-BTC-302 ab.
- First HER2-targeted therapy authorized in EU for HER2-positive BTC
- Strong efficacy with 51.6% response rate in IHC 3+ tumor patients
- Durable response with median duration of 14.9 months
- Impressive median overall survival of 18.1 months in IHC 3+ patients
- Manageable safety profile with most adverse reactions being manageable
- Expanded market reach covering EU Member States, Iceland, Norway, and Liechtenstein
- Approval is conditional and requires confirmation through Phase 3 trial
- Serious adverse reactions occurred in 16.1% of patients
- Limited to second-line treatment after prior therapy failure
Insights
Jazz's Ziihera approval marks first EU-authorized HER2-targeted therapy for biliary tract cancer with impressive efficacy data.
The European Commission's conditional marketing authorization for Ziihera (zanidatamab) represents a significant advancement in the treatment landscape for HER2-positive biliary tract cancer (BTC). This approval is particularly noteworthy as it introduces the first HER2-targeted therapy authorized specifically for this patient population in the European Union.
The HERIZON-BTC-01 trial data supporting this approval is compelling. In patients with IHC 3+ tumors, Ziihera demonstrated a confirmed objective response rate of 51.6% with a median duration of response of 14.9 months and median overall survival of 18.1 months. These are remarkable outcomes considering the historical context of BTC, where second-line treatments typically yield response rates below 10% and median survival of only 6-9 months.
Mechanistically, zanidatamab's unique bispecific antibody design allows it to simultaneously bind two distinct epitopes on HER2, resulting in enhanced receptor clustering, internalization, and degradation compared to traditional monoclonal antibodies. This dual-binding approach triggers multiple mechanisms of action including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.
The safety profile appears manageable, with diarrhea (
This approval highlights the growing importance of molecular profiling in biliary tract cancers, as approximately
The ongoing Phase 3 HERIZON-BTC-302 trial, which is evaluating zanidatamab in combination with standard-of-care therapy in the first-line setting, could further expand the therapeutic potential of this agent if positive. This represents a paradigm shift toward biomarker-driven approaches in gastrointestinal cancers that have historically had limited treatment options.
鈥� Conditional approval based on positive results from the HERIZON-BTC-01 Phase 2b trial 鈥�
BTCs, which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA), are a rare and aggressive group of cancers,3 with most cases diagnosed at an advanced stage4 when curative surgery is no longer an option.5,6,7 Globally, approximately
Ziihera听is the first HER2-targeted therapy given conditional authorization for HER2-positive BTC in the European Union (EU). Continued approval for this indication is contingent upon verification and description of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 trial, which is evaluating zanidatamab in combination with standard-of-care therapy versus standard-of-care therapy alone in the first-line setting for patients with HER2-positive BTC.10
"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," said Arndt Vogel, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School,
The EC decision is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated Ziihera听in patients with previously treated, unresectable, locally advanced or metastatic HER2-positive BTC. This is the largest Phase 2b trial conducted to date specifically in this population.11,12听The study enrolled 87 patients, including 80 in Cohort 1 with centrally confirmed HER2-positive tumors (IHC 2+/ISH+ [n=18] or IHC 3+/ISH+ [n=62]). The trial achieved its primary endpoint of confirmed objective response rate (cORR) in Cohort 1, as assessed by independent central review (ICR). At a median follow-up of 21.9 months, zanidatamab demonstrated听a cORR of
Findings from a pre-specified subgroup analysis in patients with IHC 3+ tumors (n=62) showed that Ziihera demonstrated a cORR of
The recommended dose of Ziihera is 20 mg/kg, administered as an intravenous infusion every two weeks until disease progression or unacceptable toxicity.2
The safety profile for zanidatamab听was evaluated in 87 patients with HER2-positive BTC (Cohorts 1 and 2) in HERIZON-BTC-01. The most common adverse reactions in this population were diarrhea (
"This conditional approval represents significant progress for the patients we serve who have been diagnosed with advanced HER2-positive BTC," 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 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."
"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," said Zorana Maravic, chief executive officer at Digestive Cancers Europe (DiCE). "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."
The European Commission听authorization extends to all European Union Member States, as well as听Iceland,听Norway, and听Liechtenstein.
For a full list of side effects and information on dosage and administration, contraindications, and other precautions when using Ziihera, please refer to the听Summary of Product Characteristics听for further information.
础产辞耻迟听窜颈颈丑别谤补庐听(锄补苍颈诲补迟补尘补产)
Ziihera听(锄补苍颈诲补迟补尘补产) is a dual HER2-targeted bispecific antibody that simultaneously binds extracellular domains 2 and 4 on separate HER2 monomers (binding in trans). Binding of zanidatamab with HER2 results in internalization leading to a reduction of the receptor on the cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and tumor cell death.2
On November 20, 2024, in the United States,听the U.S.听Food and Drug Administration (FDA) granted accelerated approval of Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.13 This accelerated approval was granted based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 confirmatory trial.13听It also received conditional approval from
Zanidatamab is also being investigated in multiple other clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by听Jazz听and BeOne Medicines Ltd. (formerly BeiGene, Ltd) under license agreements from Zymeworks, which first developed the molecule. Jazz has rights to commercialize zanidatamab in the
The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the听European Medicines Agency听for the treatment of BTC and gastric cancer.听
About Biliary Tract Cancer
Biliary tract cancers (BTC), which include gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, are rare and aggressive epithelial tumors often associated with poor prognosis.3,14听Although they account for less than
Because early symptoms are often vague or nonspecific, most BTCs are diagnosed at an advanced stage,4听when curative surgery is not an option.5,6,7听While chemotherapy and, more recently, immunotherapy-based combinations are used in the first-line setting, disease progression is common. In the absence of molecular profiling, treatment options following first-line therapy are largely limited to chemotherapy.5,6,15
HER2 overexpression or amplification defines a distinct molecular subtype of BTC16 and is observed in approximately
About听Jazz Pharmaceuticals plc听
Jazz Pharmaceuticals plc听(Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases 鈥� often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in听Dublin, Ireland听with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit听www.jazzpharmaceuticals.com for more information.
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References听
鈥�听IHC3+ stands for ImmunoHistoChemistry 3+ and refers to the highest level of HER2 protein overexpression in cancer cells
1听European Medicines Agency. Conditional marketing authorisation. European Medicines Agency website. Accessed July 1, 2025. Available at:听
2 Ziihera Summary of Product Characteristics (SmPC).
3听Mirallas O, L贸pez-Valbuena D, Garc铆a-Illescas D, et al. Advances in the systemic treatment of therapeutic approaches in biliary tract cancer.听ESMO Open. 2022;7(3):100503. doi:10.1016/j.esmoop.2022.100503.
4听Rimassa, L., Khan, S., Koerkamp, B. G., Roessler, S.,et al. Mapping the landscape of biliary tract cancer in
5听Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up.听Ann Oncol. 2023;34(2):127-40. doi:10.1016/j.annonc.2022.10.506.
6听Chakrabarti, S., Kamgar, M., Mahipal, A. Targeted therapies in advanced biliary tract cancer: an evolving paradigm.听Cancers. 2020;12(8), 2039. doi.org/10.3390/cancers12082039.
7听Valle JW, Kelley RK, et al. Biliary tract cancer.听Lancet. 2021;397(10272):428-44. doi:10.1016/S0140-6736(21)00153-7.
8听Galdy S, Lamarca A, et al. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastas Rev. 2017; doi: 10.1007/s10555-016-9645-x.
9听Vivaldi, C. HER2 overexpression as a poor prognostic determinant in resected biliary tract cancer. Oncologist. 2020;25(10):886-893. doi:10.1634/theoncologist.2019-0922.
10听ClinicalTrials.gov. Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer. Updated June 24, 2025. Accessed July 1, 2025. Available at:听
11听Pant, S et al. Zanidatamab in Previously Treated HER2-Positive Biliary Tract Cancer: Overall Survival and Longer Follow-Up From the Phase 2b HERIZON-BTC-01 Study. J Clin Oncol. 2024; 42(16_suppl). Abstract 4091.
12听Harding J, Fan J, Oh D-Y, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study.听Lancet Oncol. 2023;24(7):772-82. doi:10.1016/S1470-2045(23)00242-5.
13听U.S. Food and Drug Administration. Ziihera庐 (zanidatamab-hrii)听 prescribing information. Accessdata.fda.gov. Updated November 2024. Accessed July 1, 2025.
14听Kam A, et al. Current and emerging therapies for advanced biliary tract cancers.听Lancet Gastroenterol Hepatol. 2021;6(11):956-69. doi:10.1016/S2468-1253(21)00171-0.
15听Lamarca, A., Hubner, R. A., Ryder, W. D., et al. Second-line chemotherapy in advanced biliary cancer: a systematic review.听Annals of Oncology. 2025;听25(12), 2328-2338. doi.org/10.1093/annonc/mdu162.
16听Hechtman, J. F., Liu, W., Sadowska, J.,et al. Sequencing of 279 cancer genes in ampullary carcinoma reveals trends relating to histologic subtypes and frequent amplification and overexpression of ERBB2 (HER2).听Modern Pathology. 2015;28(8), 1123-1129. 听doi: 10.1038/modpathol.2015.57.
17听Jazz Pharmaceuticals, Inc, Data on file.
听
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