Ziihera, the first and only FDA-approved dual HER2-targeted bispecific antibody for HER2+ (IHC 3+) BTC, is now commercially available in the United States

Ziihera是FDA批准的第一个也是唯一一个针对HER2+（IHC 3+）BTC的双重HER2靶向双特异性抗体，现已在美国上市

For U.S. media and investors only

仅限美国媒体和投资者

DUBLIN, Dec. 5, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that zanidatamab-hrii (Ziihera®) 50 mg/mL for injection for intravenous use is recommended by the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 2A treatment option for Biliary Tract Cancers (BTC)..

都柏林，2024年12月5日/PRNewswire/--Jazz Pharmaceuticals plc（纳斯达克股票代码：Jazz）今天宣布，国家综合癌症网络®（NCCN®）肿瘤学临床实践指南（NCCN Guidelines®）推荐50 mg/mL注射用扎尼达单抗hrii（Zihera®）作为胆道癌（BTC）的2A类治疗选择。。

Ziihera was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on November 20, 2024, for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test. The FDA approval of Ziihera was based on results from the HERIZON-BTC-01 clinical trial including a 52% objective response rate and median duration of response of 14.9 months as determined by independent central review (ICR).

Ziihera于2024年11月20日获得美国食品和药物管理局（FDA）的加速批准，用于治疗先前接受过治疗的，不可切除的或转移性HER2阳性（IHC 3+）BTC的成年人，如FDA批准的测试所检测。FDA批准Ziihera是基于HERIZON-BTC-01临床试验的结果，包括52%的客观缓解率和14.9个月的中位缓解期，由独立中央审查（ICR）确定。

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 Ziihera is now commercially available to prescribers and customers in the U.S. and is available for purchase from authorized Specialty Distributors..

是否继续批准该适应症可能取决于验证性试验中对临床益处的验证和描述。1 Ziihera现在可在美国的处方药和客户中商购，并可从授权的专业分销商处购买。。

'The addition of Ziihera to the NCCN Guidelines® in Oncology reaffirms the importance of this advancement in treating BTC and supports our commitment to ensuring that HER2-positive BTC patients, through their health care professionals, can access this important new therapeutic option,' said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals.

Jazz Pharmaceuticals执行副总裁、全球研发总监兼首席医疗官Rob Iannone医学博士说：“在NCCN肿瘤学指南®中增加Ziihera重申了这一进步在治疗BTC方面的重要性，并支持我们确保HER2阳性BTC患者通过其医疗保健专业人员获得这一重要的新治疗选择的承诺。”。

'Ziihera is the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC – a disease with a poor prognosis and limited treatment options. We are excited to deliver this new treatment option to patients in the United States following its accelerated approval.'.

“Ziihera是第一个也是唯一一个针对BTC患者的双重HER2靶向双特异性抗体和无化疗治疗方法，BTC是一种预后不良且治疗选择有限的疾病。在加速批准后，我们很高兴为美国患者提供这种新的治疗选择。”。

The NCCN Guidelines play a pivotal role in decision-making processes for individuals involved in cancer care all over the world, including physicians, nurses, pharmacists, payers, and patients and their families. The guidelines present expert recommendations for cancer screening, diagnosis and treatment, as well as cancer care options, and is utilized in cancer treatment decision-making to drive positive patient outcomes..

。该指南为癌症筛查，诊断和治疗以及癌症护理选择提供了专家建议，并用于癌症治疗决策，以推动患者取得积极的结果。。

The NCCN is a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to defining and advancing quality, effective, equitable, and accessible cancer care and prevention so all people can live better lives.

NCCN是一个由33个主要癌症中心组成的非营利性联盟，致力于患者护理，研究和教育。NCCN致力于定义和提高质量，有效，公平和可获得的癌症护理和预防，以便所有人都能过上更好的生活。

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

NCCN对其内容、使用或应用不作任何形式的保证，也不以任何方式对其应用或使用承担任何责任。

More information about Ziihera, the Full Prescribing Information, including Boxed Warning and Patient Information, is available here.

有关Ziihera的更多信息，完整的处方信息，包括盒装警告和患者信息，可在此处获得。

About Ziihera® (zanidatamab-hrii)Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

关于Ziihera®（zanidatamab hrii）Ziihera（zanidatamab hrii）是一种双特异性HER2定向抗体，可与HER2上的两个细胞外位点结合。扎尼达单抗hrii与HER2的结合导致内化，导致肿瘤细胞表面受体的减少。Zanidatamab hrii诱导补体依赖性细胞毒性（CDC），抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）。

These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.1 In the United States, Ziihera is indicated 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.1 The U.S. Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response.

这些机制导致体外和体内肿瘤生长抑制和细胞死亡。在美国，Ziihera用于治疗先前治疗过的，不可切除的或转移性HER2阳性（IHC 3+）胆道癌（BTC）的成年人，如FDA批准的测试所检测到的。S、 美国食品和药物管理局（FDA）根据总体反应率和反应持续时间批准了该适应症的加速批准。

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1.

继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。

Zanidatamab is not approved anywhere else in the world.

Zanidatamab在世界其他任何地方都没有获得批准。

Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

Zanidatamab正在多项临床试验中开发，作为表达HER2的实体瘤患者的靶向治疗选择。Zanidatamab是由Jazz和BeiGene，Ltd.（BeiGene）根据Zymeworks的许可协议开发的，Zymeworks是该分子的首家开发公司。

The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2-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 first line gastroesophageal adenocarcinoma (GEA).

FDA批准了先前接受过HER2扩增BTC治疗的患者的扎尼达单抗开发突破性治疗方案，以及扎尼达单抗的两种快速治疗方案：一种作为难治性BTC的单一药物，另一种与一线胃食管腺癌（GEA）的标准治疗化疗相结合。

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关于治疗BTC和GEA的孤儿药指定，以及欧洲药品管理局关于治疗BTC和胃癌的孤儿药指定。。

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITYExposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patientsof the risk and need for effective contraception.

警告：胚胎-胎儿毒性怀孕期间暴露于ZIIHERA可能会导致胚胎-胎儿伤害。告知患者有效避孕的风险和必要性。

WARNINGS AND PRECAUTIONS

警告和注意事项

Embryo-Fetal ToxicityZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death..

胚胎胎儿毒性当给予孕妇时，IIHera会导致胎儿伤害。在文献报道中，怀孕期间使用HER2定向抗体会导致羊水过少和羊水过少序列的病例，表现为肺发育不全，骨骼异常和新生儿死亡。。

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA..

在ZIIHERA开始之前，验证具有生殖潜力的女性的妊娠状况。建议具有生殖潜力的孕妇和女性在怀孕期间或怀孕前4个月内接触ZIIHERA可能会导致胎儿伤害。建议有生殖潜力的女性在使用ZIIHERA治疗期间和最后一剂ZIIHERA后4个月内使用有效的避孕措施。。

Left Ventricular DysfunctionZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7).

左心室功能障碍可导致左心室射血分数（LVEF）降低。233例患者中，4.3%的患者LVEF下降>10%，降至<50%。据报道，0.9%的患者左心室功能障碍（LVD）导致ZIIHERA永久停药。首次发生LVD的中位时间为5.6个月（范围：1.6至18.7）。

LVD resolved in 70% of patients..

70%的患者LVD消退。。

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

在开始ZIIHERA之前和治疗期间定期评估LVEF。根据不良反应的严重程度，停止服用或永久停用ZIIHERA。

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

基线射血分数低于50%的患者尚未确定ZIIHERA的安全性。

Infusion-Related ReactionsZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients.

输液相关反应Ziihera可引起输液相关反应（IRR）。在临床研究中，233名接受ZIIHERA作为单一药物治疗的患者中有31%报告了IRR，包括3级（0.4%）和2级（25%）。0.4%的患者报告了导致ZIIHERA永久停药的内部收益率。

IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day..

；97%的内部收益率在一天内解决。。

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use..

在每次服用ZIIHERA之前，进行术前用药以预防潜在的IRR。在ZIIHERA给药期间以及输注完成后根据临床指示监测患者的IRR体征和症状。有治疗IRR的药物和急救设备可立即使用。。

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

如果发生内部收益率，减慢或停止输注，并进行适当的医疗管理。在恢复之前，监测患者直至体征和症状完全消失。对于复发性严重或危及生命的IRR患者，永久停用ZIIHERA。

DiarrheaZIIHERA can cause severe diarrhea.

腹泻可引起严重腹泻。

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity..

在临床研究中接受治疗的233例患者中，有48%报告有腹泻，包括3级（6%）和2级（17%）。如果发生腹泻，根据临床指示进行止泻治疗。按照临床指示进行诊断测试，以排除其他腹泻原因。根据严重程度扣留或永久停用ZIIHERA。。

ADVERSE REACTIONSSerious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%).

不良反应接受ZIIHERA治疗的80例不可切除或转移性HER2阳性BTC患者中，53%发生严重不良反应。。

A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA..

一名接受ZIIHERA治疗的患者发生了致命的肝衰竭不良反应。。

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

80例接受ZIIHERA（≥20%）治疗的不可切除或转移性HER2阳性BTC患者最常见的不良反应为腹泻（50%），输注相关反应（35%），腹痛（29%）和疲劳（24%）。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

Pediatric UseSafety and efficacy of ZIIHERA have not been established in pediatric patients.

尚未在儿科患者中确定ZIIHERA的儿科使用安全性和有效性。

Geriatric UseOf the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

老年人使用ZIIHERA治疗不可切除或转移性HER2阳性BTC的80例患者中，有39例（49%）65岁及以上的患者。37名（46%）年龄在65-74岁之间，2名（3%）年龄在75岁或以上。

No overall differences in safety or efficacy were observed between these patients and younger adult patients.

这些患者与年轻成年患者之间在安全性或有效性方面没有观察到总体差异。

About Biliary Tract CancerBTC, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers globally and are often associated with a poor prognosis.2,3 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers.

关于胆道癌，包括胆囊癌和肝内外胆管癌，占全球所有成人癌症的1%以下，通常与预后不良有关[2,3]。人类表皮生长因子受体2（HER2）是其他癌症抗肿瘤治疗的有效靶点。

Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.4,5,6,7.

在美国各地。S、 ，欧洲和日本，每年约有12000人被诊断出患有HER2+BTC。4,5,6,7。

About Jazz PharmaceuticalsJazz Pharmaceuticals plc (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 life-changing medicines for people with serious diseases—often with limited or no therapeutic options.

关于Jazz PharmaceuticalsJazz Pharmaceuticals plc（纳斯达克：Jazz）是一家全球生物制药公司，其宗旨是创新，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开发改变生命的药物，这些疾病通常只有有限的或没有治疗选择。

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.

我们有多种上市药物，包括治疗睡眠障碍和癫痫的领先疗法，以及不断增长的癌症治疗组合。我们以患者为中心，以科学为驱动的方法，在我们强大的肿瘤学和神经科学创新疗法管道中推动了开创性的研究和开发进展。

Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information..

Jazz总部位于爱尔兰都柏林，在多个国家拥有研发实验室、制造设施和员工，致力于为全球患者提供服务。有关更多信息，请访问www.jazzpharmaticals.com。。

Contacts:

联系人：

Jazz Media Contact:Kristin BhavnaniHead of Global Corporate CommunicationsJazz Pharmaceuticals plcCorporateAffairsMediaInfo@jazzpharma.comIreland +353 1 637 2141U.S. +1 215 867 4948

Jazz媒体联系人：Kristin Bhavnani Jazz Pharmaceuticals全球企业传播负责人plcCorporateAffairsMediaInfo@jazzpharma.comIreland+353 1 637 2141U。S、 +1 215 867 4948

Jazz Investor Contact:Jeff MacdonaldExecutive Director, Investor RelationsJazz Pharmaceuticals plcinvestorinfo@jazzpharma.comIreland +353 1 634 3211        U.S. +1 650 496 2717

Jazz投资者联系人：Jeff MacDonald投资者关系执行董事Azz Pharmaceuticalsplcinvestorinfo@jazzpharma.comIreland+353 1 634 3211美国+1 650 496 2717

References:

参考文献：

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1 ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.2 Valle JW, et al. Lancet 2021; 397:428-443 Siegel RL, et al. CA Cancer J Clin 2022; 72;7-334 BTC overall diagnosed patients as per SEER 22.5 Assumes anatomic subsites intrahepatic CCA, extrahepatic CCA, gallbladder cancer, and BTC unspecified.6 Assumes HER2 positivity rates per anatomical subsite from Galdy, S., Lamarca, A., McNamara, M.G.

1 ZIIHERA（zanidatamab hrii）处方信息。加利福尼亚州帕洛阿尔托：Jazz Pharmaceuticals，Inc.2 Valle JW等人，《柳叶刀》2021；397:428-443 Siegel RL等人，《CA癌症J临床2022》；72；根据SEER 22.5，7-334 BTC总体诊断患者假设解剖亚位点肝内CCA，肝外CCA，胆囊癌和BTC未指定。6假设每个解剖亚位点的HER2阳性率来自Galdy，S.，Lamarca，A.，McNamara，M.G。

et al. Cancer Metastasis Rev 36, 141–157 (2017), Nobuyoshi Hiraoka, et al. Human Pathology, Volume 105, 2020, Pages 9-197 Major markets: UK, France, Germany, Spain, Italy. Note: HER2+ BTC patients in Jazz-controlled commercial territories, which includes Japan, and excludes other certain Asia Pacific countries licensed to BeiGene, Ltd.

等人，《癌症转移》第36141-157版（2017年），平冈信义等人，《人类病理学》，第1052020卷，第9-197页主要市场：英国、法国、德国、西班牙、意大利。注：爵士乐控制的商业地区（包括日本）的HER2+BTC患者，不包括许可给BeiGene，Ltd的其他某些亚太国家。

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