Jazz Pharmaceuticals plc today announced that the European Commission (EC) has granted conditional marketing authorization

Jazz Pharmaceuticals plc今天宣布，欧洲委员会（EC）已授予有条件营销授权

for Ziihera

给Ziihera

(zanidatamab), a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, as monotherapy for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC 3+)

（扎尼达单抗），一种双重靶向人表皮生长因子受体2（HER2）的双特异性抗体，作为单药治疗不可切除的局部晚期或转移性HER2阳性（IHC 3+）成人患者。

biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy.

先前接受过至少一线系统治疗的胆道癌 (BTC)。

BTCs, which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA), are a rare and aggressive group of cancers,

BTC包括胆囊癌（GBC）和胆管癌（CCA），是一组罕见且侵袭性强的癌症，

with most cases diagnosed at an advanced stage

大多数病例在晚期才被诊断出来

when curative surgery is no longer an option.

当治愈性手术不再是一种选择时。

Globally, approximately 26% of patients with BTC are HER2-positive,

全球范围内，大约26%的BTC患者为HER2阳性，

a biomarker associated with poorer outcomes compared to HER2-negative disease.

与HER2阴性疾病相比，与较差结果相关的生物标志物。

Ziihera

梓赫拉

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..

是欧盟（EU）首个获得HER2阳性BTC条件性授权的HER2靶向疗法。该适应症的持续批准取决于正在进行的3期临床试验HERIZON-BTC-302中临床获益的验证和描述，该试验正在评估扎尼达单抗联合标准治疗与单独标准治疗在HER2阳性BTC一线治疗中的效果。

'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

“HER2阳性胆道癌患者在一线治疗后病情进展，面临严峻的预后，治疗选择有限，耐受性差，中位总生存期仅为六到九个月，”表示。

Arndt Vogel

阿恩特·福格尔

, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School,

医学博士，汉诺威医学院胃肠病学、肝病学和内分泌学系高级管理顾问及教授，

Germany

德国

. '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.'.

“Zanidatamab 为这一人群提供了亟需的靶向单药治疗，在 HERIZON-BTC-01 试验中，它展现了具有临床意义且持久的反应，并且安全性可控。这些数据代表了对历史上预后较差的患者的可喜进展，同时突显了在胆道癌中进行 HER2 检测的重要性，以确保符合条件的患者被识别出来接受基于生物标志物的治疗。”

The EC decision is based on data from the Phase

欧盟的决定是基于第三阶段的数据。

2b

2b

HERIZON-BTC-01 trial, which evaluated

HERIZON-BTC-01 试验，该试验评估了

Ziihera

梓赫拉

in patients with previously treated, unresectable, locally advanced or metastatic HER2-positive BTC. This is the largest Phase

在先前接受过治疗、无法切除、局部晚期或转移性的HER2阳性胆道癌患者中。这是规模最大的三期

2b

2b

trial conducted to date specifically in this population.

迄今为止，专门针对这一人群进行的试验。

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 a cORR of 41.3% (95% CI: 30.4, 52.8), including two complete responses..

该研究招募了87名患者，其中80名属于队列1，这些患者经中心确认为HER2阳性肿瘤（IHC 2+/ISH+ [n=18] 或 IHC 3+/ISH+ [n=62]）。试验达到了其主要终点，即由独立中心评审（ICR）评估的队列1中确认的客观缓解率（cORR）。在中位随访21.9个月时，Zanidatamab显示出41.3%的cORR（95% CI: 30.4, 52.8），其中包括两例完全缓解。

The median duration of response (DOR) was 14.9 months (95% CI: (7.4, not reached), and the median overall survival (OS) was 15.5 months (95% CI: 10.4, 18.5).

反应持续时间（DOR）的中位数为14.9个月（95%置信区间：7.4，未达到），总生存期（OS）的中位数为15.5个月（95%置信区间：10.4，18.5）。

Findings from a pre-specified subgroup analysis in patients with IHC 3+ tumors (n=62) showed that

预先指定的亚组分析（IHC 3+ 肿瘤患者，n=62）结果显示

Ziihera

紫罗兰

demonstrated a cORR of 51.6% (95% CI: 38.6, 64.5), with a median DOR of 14.9 months (95% CI: 7.4, 24.0).

展示了51.6%的cORR（95%置信区间：38.6, 64.5），中位DOR为14.9个月（95%置信区间：7.4, 24.0）。

The median OS in this subgroup was 18.1 months (95% CI: 12.2, 22.9).

该亚组的中位 OS 为 18.1 个月（95% CI：12.2，22.9）。

The recommended dose of

推荐剂量为

Ziihera

兹赫拉

is 20 mg/kg, administered as an intravenous infusion every two weeks until disease progression or unacceptable toxicity.

每两周一次，以20毫克/千克的剂量通过静脉输注给药，直至疾病进展或出现不可接受的毒性。

The safety profile for zanidatamab 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 (46%), infusion-related reaction (33.3%), abdominal pain (26.4%), anemia (25.3%) and fatigue (24.1%). Serious adverse reactions occurred in 16.1% of patients.

在HERIZON-BTC-01研究中，对87名HER2阳性胆道癌（BTC）患者（队列1和2）进行了扎尼达单抗的安全性评估。该人群中最常见的不良反应为腹泻（46%）、输液相关反应（33.3%）、腹痛（26.4%）、贫血（25.3%）和疲劳（24.1%）。严重不良反应发生在16.1%的患者中。

The most frequent serious adverse reactions were diarrhea (2.3%), fatigue (2.3%), and increased alanine aminotransferase (2.3%)..

最常见的严重不良反应是腹泻 (2.3%)、疲劳 (2.3%) 和丙氨酸氨基转移酶升高 (2.3%)。

'This conditional approval represents significant progress for the patients we serve who have been diagnosed with advanced HER2-positive BTC,' said

“这一有条件的批准对我们服务的那些被诊断为晚期HER2阳性BTC的患者而言，代表了显著的进展，”

Robert Iannone

罗伯特·伊安诺内

, MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. '

医学博士，理学硕士，爵士制药公司执行副总裁，全球研发主管兼首席医疗官。'

Ziihera

齐赫拉

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.

是欧盟首个专门针对这一人群的HER2靶向疗法，欧洲委员会的决定反映了HERIZON-BTC-01数据的强大说服力以及在罕见胃肠道癌症中创新的紧迫性。这一里程碑进一步巩固了我们推进以生物标志物为导向的治疗策略的决心，这些疗法旨在满足严重未满足的需求并改善患者预后。

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.'.

我们正在积极招募一线HER2阳性胆道癌的全球三期临床试验，并继续探索扎尼达单抗在其他HER2表达肿瘤中的潜力。

'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

“胆道癌在全球范围内变得越来越常见，并且越来越多地影响60岁以下的人群，造成了显著的社会和经济负担，”

Zorana Maravic

佐拉纳·马拉维奇

, 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.

欧洲消化道癌症组织（DiCE）首席执行官。“这些癌症通常在晚期才被诊断出来，患者可选择的治疗方案有限，不幸的是，他们的病情常常会进一步恶化。

Ziihera

兹赫拉

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.'

为HER2阳性BTC患者在此阶段提供了急需的化疗替代方案。同时也为消化道癌症患者群体带来了希望，这是扩大靶向治疗可及性的又一步。

The European Commission authorization extends to all European Union Member States, as well as Iceland, Norway, and Liechtenstein.

欧盟委员会的授权范围涵盖所有欧盟成员国，以及冰岛、挪威和列支敦士登。

For a full list of side effects and information on dosage and administration, contraindications, and other precautions when using

有关副作用的完整列表以及使用时的剂量和用法、禁忌症及其他注意事项的信息，

Ziihera

齐赫拉

, please refer to the Summary of Product Characteristics for further information.

，请参阅产品特性摘要以获取更多信息。

About Ziihera

关于Ziihera

®

®

(zanidatamab)

(扎尼达单抗)

Ziihera

梓赫拉

(zanidatamab) 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).

扎尼达单抗是一种双重HER2靶向的双特异性抗体，能够同时结合在不同HER2单体上的胞外结构域2和4（跨膜结合）。扎尼达单抗与HER2的结合会导致内化，从而减少细胞表面的受体数量。扎尼达单抗可诱导补体依赖性细胞毒性（CDC）、抗体依赖性细胞毒性（ADCC）以及抗体依赖性细胞吞噬作用（ADCP）。

These mechanisms result in tumor growth inhibition and tumor cell death..

这些机制导致肿瘤生长抑制和肿瘤细胞死亡。

November 20, 2024

2024年11月20日

, in the United States, the U.S. Food and Drug Administration (FDA) granted accelerated approval of

在美国，美国食品和药物管理局 (FDA) 授予加速批准了

Ziihera

梓赫拉

(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.

（zanidatamab-hrii）用于治疗先前接受过治疗、无法切除或转移性的HER2阳性（IHC 3+）胆道癌（BTC）成年患者，需通过FDA批准的检测方法检测。

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.

此次加速批准是基于客观缓解率和缓解持续时间。该适应症的持续批准可能取决于正在进行的III期HERIZON-BTC-302确证性试验中对临床获益的验证和描述。

It also received conditional approval from

它还获得了有条件批准

China's

中国的

National Medical Products Administration (NMPA) in

国家药品监督管理局（NMPA）在

May 2025

2025年5月

for the treatment of patients with previously treated, unresectable or metastatic HER2+BTC. Continued approval of this indication will depend on the verification of clinical benefit in the patient population through an ongoing confirmatory trial.

用于治疗既往接受过治疗、不可切除或转移性的HER2+胆道癌患者。该适应症的持续批准将取决于通过正在进行的确证性试验在患者群体中验证临床获益。

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 Jazz and BeOne Medicines Ltd. (formerly BeiGene, Ltd) under license agreements from Zymeworks, which first developed the molecule.

Zanidatamab 还在多项其他临床试验中作为针对表达 HER2 的实体瘤患者的靶向治疗选择进行研究。Zanidatamab 由 Jazz 和 BeOne Medicines Ltd.（前身为百济神州有限公司）根据与最初开发该分子的 Zymeworks 的许可协议进行开发。

Jazz has rights to commercialize zanidatamab in the U.S., .

Jazz拥有在美国将zanidatamab商业化的权利。

and all other territories except for those

以及除上述以外的所有其他领土

Asia/Pacific

亚洲/太平洋地区

territories that Zymeworks previously licensed to BeiGene, Ltd. [which are

Zymeworks 之前授权给百济神州有限公司的领土 [包括

Asia

亚洲

(excluding

（不包括

Japan

日本

Australia

澳大利亚

and

和

New Zealand

新西兰

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).

FDA授予zanidatamab在既往接受过治疗的HER2基因扩增型BTC患者中的突破性疗法资格，并给予zanidatamab两项快速通道资格：一项是作为单药治疗难治性BTC，另一项是与标准护理化疗联合用于一线胃食管腺癌（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 European Medicines Agency for the treatment of BTC and gastric cancer. .

此外，zanidatamab 已获得 FDA 授予的用于治疗 BTC 和 GEA 的孤儿药资格，以及欧洲药品管理局授予的用于治疗 BTC 和胃癌的孤儿药资格。

About Biliary Tract Cancer

关于胆道癌

Biliary tract cancers (BTC), which include gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, are rare and aggressive epithelial tumors often associated with poor prognosis.

胆道癌 (BTC) 包括胆囊癌、肝内胆管癌和肝外胆管癌，是罕见且侵袭性的上皮肿瘤，通常预后较差。

Although they account for less than 1% of all human cancers, cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma and comprises approximately 10–15% of all primary liver cancers. Global mortality from BTC has risen in recent decades.

虽然胆管癌占所有人类癌症的比例不到1%，但它是继肝细胞癌之后第二常见的原发性肝癌，约占所有原发性肝癌的10-15%。近年来，BTC的全球死亡率有所上升。

Because early symptoms are often vague or nonspecific, most BTCs are diagnosed at an advanced stage,

由于早期症状通常模糊或不具特异性，大多数BTC在晚期才被诊断出来，

when curative surgery is not an option.

当治愈性手术不是一个选项时。

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.

虽然化疗以及最近的免疫治疗联合方案被用于一线治疗，但疾病进展仍然常见。在缺乏分子谱分析的情况下，一线治疗后的选择基本上局限于化疗。

HER2 overexpression or amplification defines a distinct molecular subtype of BTC

HER2过表达或扩增定义了BTC的一种独特分子亚型。

and is observed in approximately 26% of patients globally.

并且在全球大约26%的患者中被观察到。

HER2-positive BTC is associated with worse prognosis than HER2-negative disease.

HER2阳性的BTC预后比HER2阴性疾病更差。

Across the U.S.,

美国各地，

Europe

欧洲

, and

，以及

Japan

日本

, an estimated 12,000 people are diagnosed with HER2-positive BTC each year.

每年约有12,000人被诊断出患有HER2阳性胆道癌。

About Jazz Pharmaceuticals plc

关于Jazz制药公司

Jazz Pharmaceuticals plc (Nasdaq:

Jazz Pharmaceuticals plc（纳斯达克：

) 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 – 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.

）是一家全球生物制药公司，其宗旨是通过创新来改变患者及其家人的生活。我们致力于为患有严重疾病的人群开发可能改变生命的药物——这些疾病通常缺乏或没有任何治疗选择。我们拥有多种已上市的药物组合，包括针对睡眠障碍和癫痫的领先疗法，并且我们的癌症治疗药物组合也在不断增长。

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 Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide.

我们以患者为中心、以科学为驱动的方法，推动了在肿瘤学和神经科学领域众多创新疗法的前沿研发进展。Jazz 总部位于爱尔兰都柏林，在多个国家设有研发实验室、生产设施和员工，致力于为全球患者服务。