DUBLIN, Nov. 20, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced the U.S. Food and Drug Administration (FDA) accelerated approval of Ziihera® (zanidatamab-hrii) 50mg/mL for injection for intravenous use 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 Ziihera was approved under accelerated approval based on a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months as determined by independent central review (ICR).

都柏林，2024年11月20日/PRNewswire/--Jazz Pharmaceuticals plc（纳斯达克：Jazz）今天宣布，美国食品和药物管理局（FDA）加速批准注射用Zihera®（zanidatamab hrii）50mg/mL用于静脉注射，用于治疗FDA批准的试验检测到的先前接受过治疗的，不可切除的或转移性HER2阳性（IHC 3+）胆道癌（BTC）的成年人。1 Zihera根据独立中央审查（ICR）确定的52%客观缓解率（ORR）和中位缓解期（DOR）为14.9个月的加速批准。

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The Phase 3 HERIZON-BTC-302 confirmatory trial is ongoing to evaluate 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. .

是否继续批准该适应症可能取决于验证性试验中临床获益的验证和描述[1]。第3阶段HERIZON-BTC-302验证性试验正在进行中，以评估扎尼达单抗联合标准护理治疗与标准护理治疗单独用于HER2阳性BTC患者的一线治疗。。

'BTC is a devastating disease with a poor prognosis and five-year survival rates under five percent in the metastatic setting. Patients with unresectable or metastatic HER2-positive BTC have had a high unmet need with limited treatment options and few approved therapies,' 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. 'The approval of Ziihera, which previously received Breakthrough Therapy Designation from the FDA for this indication, is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC.

“BTC是一种毁灭性疾病，预后不良，在转移性环境中五年生存率低于5%。Jazz Pharmaceuticals执行副总裁、全球研发主管兼首席医疗官、医学博士Rob Iannone说，不可切除或转移性HER2阳性BTC患者的需求很高，治疗选择有限，批准的治疗很少。“Ziihera的批准是一个重要的进步，它之前曾因该适应症获得FDA的突破性治疗指定，为BTC患者提供了第一个也是唯一一个双重HER2靶向双特异性抗体和无化疗治疗。

We look forward to advancing research of zanidatamab in BTC and other HER2-expressing solid tumors, with the goal of improving outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers.'.

我们期待着推进扎尼达单抗在BTC和其他表达HER2的实体瘤中的研究，目的是改善更多被诊断患有这些难以治疗的HER2阳性癌症的人的预后。

The FDA approval of Ziihera is based on compelling data from the HERIZON-BTC-01 trial, which included the evaluation of zanidatamab as a single agent in previously treated HER2-positive (as determined by Roche Diagnostic's PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody companion diagnostic) BTC and is the largest Phase 2b clinical trial to date specifically for this patient population.

FDA对Ziihera的批准是基于来自HERIZON-BTC-01试验的令人信服的数据，该试验包括评估扎尼达单抗作为先前治疗的HER2阳性（由Roche Diagnostic's PATHWAY®anti-HER-2/neu（4B5）兔单克隆一抗伴侣诊断）BTC的单一药物，是迄今为止专门针对该患者群体的最大的2b期临床试验。

The trial achieved its primary endpoint of confirmed objective response rate (cORR) by independent central review (ICR) and results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023, published in The Lancet Oncology, and included in the 2023 Best of ASCO® program. Longer follow-up data showing improvement upon previously reported DOR were reported at the ASCO Annual Meeting 2024.1.

该试验通过独立中央审查（ICR）实现了确认客观缓解率（cORR）的主要终点，结果发表在《柳叶刀肿瘤学》杂志上的2023年美国临床肿瘤学会（ASCO）年会上，并被纳入2023年最佳ASCO®计划。ASCO 2024.1年会报告了更长时间的随访数据，显示先前报告的DOR有所改善。

'As a clinical investigator and medical oncologist focused on advancing the care of patients with biliary tract and liver cancers, I have experienced firsthand the significant unmet need for effective therapies for patients with these diseases,' said Dr. James Harding, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center.

Memorial Sloan Kettering癌症中心胃肠肿瘤学和早期药物开发服务副主治医师詹姆斯·哈丁（JamesHarding）博士说：“作为一名专注于推进胆道癌和肝癌患者护理的临床研究者和医学肿瘤学家，我亲身体验到这些疾病患者对有效治疗的巨大需求尚未得到满足。”。

'Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer.'.

“扎尼达单抗已显示出抗肿瘤活性，现在是HER2阳性胆道癌患者的新选择。我期待着为胆道癌患者继续成功开发药物。”。

'Metastatic biliary tract cancer, BTC, places a significant burden on patients, affecting their quality of life and their emotional and mental well-being, as well as that of their families,' said Stacie Lindsey, CEO and founder of the Cholangiocarcinoma Foundation. 'The approval of Ziihera offers a promising treatment option.

胆管癌基金会首席执行官兼创始人斯泰西·林赛（StacieLindsey）说：“转移性胆管癌（BTC）给患者带来了沉重负担，影响了他们的生活质量、情绪和心理健康，以及他们的家人。”Ziihera的批准提供了一个有前途的治疗选择。

It provides patients and their loved ones the possibility of more time together and an improved quality of life, which is invaluable for the entire BTC community.' .

它为患者及其亲人提供了更多时间在一起的可能性，并改善了生活质量，这对整个BTC社区来说是无价的。”。

The efficacy of Ziihera was evaluated in 62 patients with HER2-positive (IHC 3+ by central assessment) BTC in Cohort 1 of HERIZON-BTC-01, with major efficacy outcome measures of ORR and DOR as determined by ICR according to RECIST (Response Evaluation Criteria in Solid Tumors) v1.1.1 The study demonstrated an ORR of 52% [95% confidence interval (CI): 39, 65)] with a Kaplan Meier (KM) estimated median DOR of 14.9 months [95% CI: 7.4-not estimable] by ICR.1.

在HERIZON-BTC-01队列1的62例HER2阳性（IHC 3+通过中央评估）BTC患者中评估了Ziihera的疗效，根据RECIST（实体瘤反应评估标准）v1.1.1，ICR确定了ORR和DOR的主要疗效结果指标。该研究显示ORR为52%[95%置信区间（CI）：39,65]，Kaplan-Meier（KM）估计的中位DOR为14.9个月[95%CI:7.4-不可估计]。

Boxed Warning for Embryo-fetal toxicity: Exposure to Ziihera during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.1

胚胎-胎儿毒性的盒装警告：怀孕期间接触Ziihera会导致胚胎-胎儿伤害。告知患者有效避孕的风险和必要性。1

The safety profile for Ziihera has been demonstrated in 80 patients in the HERIZON-BTC-01 trial. Serious adverse reactions occurred in 53% of patients who received Ziihera. The most common adverse reactions in patients who received Ziihera (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue. 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%).

在HERIZON-BTC-01试验中，80名患者已经证明了Zihera的安全性。53%接受Ziihera治疗的患者发生严重不良反应。接受Ziihera（≥20%）的患者最常见的不良反应是腹泻，输液相关反应，腹痛和疲劳。>2%的患者出现严重不良反应，包括胆道梗阻（15%），胆道感染（8%），败血症（8%），肺炎（5%），腹泻（3.8%），胃梗阻（3.8%）和疲劳（2.5%）。

A fatal adverse reaction of hepatic failure occurred in one patient who received Ziihera. Permanent discontinuation due to an adverse reaction occurred in 2.5% of patients who received Ziihera.1 See additional safety information below and full prescribing information https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf..

一名接受Ziihera治疗的患者发生致命的肝衰竭不良反应。2.5%接受Ziihera治疗的患者因不良反应而永久停药。1请参阅下面的其他安全信息和完整的处方信息https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf..

The confirmatory, global, randomized Phase 3 trial HERIZON-BTC-302 (NCT06282575) is ongoing and 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. Continued approval for Ziihera may be contingent upon verification and description of clinical benefit in this confirmatory trial..

验证性，全球，随机3期试验HERIZON-BTC-302（NCT06282575）正在进行中，正在评估扎尼达单抗联合标准治疗与HER2阳性BTC患者一线治疗中单独标准治疗的疗效。Ziihera的继续批准可能取决于该验证性试验中临床益处的验证和描述。。

Zanidatamab is also being investigated in a number of additional tumor types, including Phase 3 trials in gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC). The HERIZON-GEA-01 trial evaluating the potential of zanidatamab plus chemotherapy with or without tislelizumab as first-line treatment for patients with advanced/metastatic HER2-positive GEAs.

Zanidatamab也正在许多其他肿瘤类型中进行研究，包括胃食管腺癌（GEA）和转移性乳腺癌（mBC）的3期临床试验。HERIZON-GEA-01试验评估了扎尼达单抗联合化疗联合或不联合tislelizumab作为晚期/转移性HER2阳性GEA患者一线治疗的潜力。

The EmpowHER-303 trial is evaluating the potential of zanidatamab in combination with physician's choice chemotherapy for the treatment of HER2-positive mBC for patients who have progressed on, or are intolerant to, previous trastuzumab deruxtecan treatment..

EmpowHER-303试验正在评估扎尼达单抗联合医师选择化疗治疗HER2阳性mBC的潜力，这些患者已经进展或不耐受以前的曲妥珠单抗-德鲁替康治疗。。

About the Phase 2b HERIZON-BTC-01 TrialThe Phase 2b HERIZON-BTC-01 trial of zanidatamab was an open-label, global Phase 2b study, which enrolled 87 patients with HER2-amplified, locally advanced unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) into 2 cohorts and included 62 patients with HER2 IHC 3+ BTC.

关于2b期HERIZON-BTC-01试验zanidatamab的2b期HERIZON-BTC-01试验是一项开放标签的全球2b期研究，纳入了87例HER2扩增，局部晚期不可切除或转移性BTC患者（胆囊癌，肝内/肝外胆管癌）分为2组，其中包括62例HER2 IHC 3+BTC患者。

The trial evaluated zanidatamab (20 mg/kg IV every 2 weeks) in patients who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. All patients were required to have HER2 status confirmed with tissue samples by a central lab. Patients (n=87) were assigned into two cohorts based on tumor IHC status: Cohort 1 (n=80) included patients who were IHC 2+/3+ (HER2-amplified) and Cohort 2 (n=7) included patients who were IHC 0/1+.

该试验评估了先前接受含吉西他滨治疗的患者的扎尼达单抗（每2周静脉注射20 mg/kg）。先前使用HER2靶向治疗的患者被排除在试验之外。所有患者都需要通过中心实验室的组织样本确认HER2状态。根据肿瘤IHC状态将患者（n=87）分为两个队列：队列1（n=80）包括IHC 2+/3+的患者（HER2扩增）和队列2（n=7）包括IHC 0/1+的患者。

Tumors were assessed every 8 weeks per RECIST v1.1. The primary endpoint was ORR by independent central review (ICR) in Cohort 1, with secondary endpoints including other efficacy and safety outcomes..

每个RECIST v1.1每8周评估一次肿瘤。主要终点是队列1中独立中央审查（ICR）的ORR，次要终点包括其他疗效和安全性结果。。

Investor Webcast on Wednesday, December 11, 2024The company will host a webcast on Wednesday, December 11, 2024, at 4:30 p.m. ET / 9:30 p.m. GMT to provide investors an overview of clinical data, patient need and commercialization strategy for Ziihera. The webcast will include commentary from a leading BTC expert and the company's senior management. .

2024年12月11日，星期三，投资者网络广播公司将于2024年12月11日，星期三，美国东部时间下午4:30/格林威治时间下午9:30举办网络广播，向投资者概述Ziihera的临床数据、患者需求和商业化策略。网络广播将包括BTC领先专家和公司高级管理层的评论。。

Audio webcast/conference call:  U.S. Dial-In Number: +1 800 715 9871 Ireland Dial-In Number: +353 1800 943 926 Additional global dial-in numbers are available here. Passcode: 4898380

音频网络广播/会议电话：美国拨入号码：+1 800 715 9871爱尔兰拨入号码：+353 1800 943 926此处提供其他全球拨入号码。密码：4898380

A live webcast of the presentation may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. Please connect to the website prior to the start of the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast.

可以从Jazz Pharmaceuticals网站（www.jazzpharmaticals.com）的投资者部分访问演示文稿的实时网络广播。请在演示开始之前连接到该网站，以确保有足够的时间下载可能需要的任何软件来收听网络广播。

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.

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。

Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response. 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 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批准了先前治疗过HER2基因扩增BTC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1L胃食管腺癌（GEA）的标准治疗化疗联合使用。

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。。

About Jazz Pharmaceuticals Jazz 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 Pharmaceuticals Jazz 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，这些患者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。。