Gallbladder Neoplasms

DUBLIN , April 25, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the conditional marketing authorization of zanidatamab, an investigational 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+)† biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy.1 "This positive CHMP opinion is a welcome step for physicians and patients in Europe who face a critical unmet need in HER2-positive biliary tract cancers, a rare and aggressive group of cancers with poor prognosis and limited treatment options," said Robert Iannone , MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals . "If approved, zanidatamab would be the first HER2-targeted therapy licensed for this difficult-to-treat cancer in the EU, marking an important milestone in addressing this unmet need. We look forward to the European Commission's decision and the opportunity to provide a new treatment option for patients." The CHMP recommendation is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated zanidatamab in previously treated, inoperable, and advanced or metastatic HER2-positive BTC.2,3 While biliary tract cancers (BTCs), which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA),4 account for less than 1% of all human cancers,5 CCA is the second most common primary liver cancer after hepatocellular carcinoma (HCC).5 It comprises approximately 10–15% of all primary liver cancers,4,5 and its global mortality rate has risen in recent decades.5 Most BTC cases are diagnosed at an advanced stage due to the vague or nonspecific nature of early disease symptoms,6 making curative surgery an option for only a minority of patients.5,7,8 Although chemotherapy and, more recently, immunotherapy-based combinations are used in the first-line setting, disease progression is common, and second-line treatment options are, in the absence of molecular analysis, largely limited to chemotherapy.5,7,9 HER2 overexpression or amplification has been identified as a distinct molecular subtype of BTC10,11 and is associated with a worse prognosis compared to HER2-negative BTC.12 Yet, no HER2-targeted therapies are currently approved for this indication in the European Union (EU). The CHMP's recommendation will now be reviewed by the European Commission which has the authority to approve medicines in all EU Member States, Iceland , Norway , and Liechtenstein , and is expected to make a final decision. About Zanidatamab 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). These mechanisms result in tumor growth inhibition and tumor cell death.13 On November 20, 2024 , in the United States, the U.S. Food and Drug Administration (FDA) granted accelerated approval of zanidatamab-hrii (Ziihera®) 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.14 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.14 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 BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule. Jazz has rights to commercialize zanidatamab in the U.S. , Europe , Japan and all other territories except for those Asia/Pacific territories that Zymeworks previously licensed to BeiGene, Ltd. [which are Asia (excluding Japan ), Australia and New Zealand ]. 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 European Medicines Agency for the treatment of BTC and gastric cancer. About Biliary Tract Cancer Biliary tract cancers (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers worldwide and are often associated with a poor prognosis.5,7 Approximately 26% of patients with BTC are HER2-positive.10 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers.7,15 Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.16 Most patients (>65%) are diagnosed with tumors that cannot be removed surgically.7 About Jazz Pharmaceuticals plc 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 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. 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. Please visit www.jazzpharmaceuticals.com for more information. Jazz Pharmaceuticals plc Caution Concerning Forward-Looking StatementsThis press release contains forward-looking statements, including, but not limited to, statements related to the European Commission's potential approval of zanidatamab for the treatment of adults with BTC in the EU and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the successful completion of regulatory activities and uncertain regulatory approval, and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2024 , and future filings and reports by Jazz Pharmaceuticals . Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Media Contact: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc CorporateAffairsMediaInfo@jazzpharma.com Ireland +353 1 637 2141 U.S. +1 215 867 4948 Investors: Jeff Macdonald Executive Director, Investor Relations Jazz Pharmaceuticals plc investorinfo@jazzpharma.com Ireland +353 1 634 3211 U.S. +1 650 496 2717 † IHC3+ stands for ImmunoHistoChemistry 3+ and refers to the highest level of HER2 protein overexpression in cancer cells References _______________________ 1 Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2025 | European Medicines Agency (EMA). European Medicines Agency (EMA). Published April 25, 2025 . Accessed April 25, 2025 . https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-22-25-april-20252 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 4091.3 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. Lancet Oncol. 2023;24(7):772-82. doi:10.1016/S1470-2045(23)00242-5.4 Mirallas O, López-Valbuena D, García-Illescas D , et al. Advances in the systemic treatment of therapeutic approaches in biliary tract cancer. ESMO Open. 2022;7(3):100503. doi:10.1016/j.esmoop.2022.100503.5 Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up. Ann Oncol. 2023;34(2):127-40. doi:10.1016/j.annonc.2022.10.506.6 Rimassa, L., Khan, S., Koerkamp, B. G., Roessler, S.,et al. Mapping the landscape of biliary tract cancer in Europe : challenges and controversies. The Lancet Regional Health–Europe. 2025; 50, 101171. doi.org/10.1016/j.lanepe.2024.1011717 Chakrabarti, S., Kamgar, M., Mahipal, A. Targeted therapies in advanced biliary tract cancer: an evolving paradigm. Cancers. 2020;12(8), 2039. doi.org/10.3390/cancers120820398 Valle JW, Kelley RK, et al. Biliary tract cancer. Lancet . 2021;397(10272):428-44. doi:10.1016/S0140-6736(21)00153-7.9 Lamarca, A., Hubner, R. A., Ryder, W. D.,et al. Second-line chemotherapy in advanced biliary cancer: a systematic review. Annals of Oncology. 2025; 25(12), 2328-2338. doi.org/10.1093/annonc/mdu16210 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-x11 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). Modern Pathology. 2015;28(8), 1123-1129. doi: 10.1038/modpathol.2015.5712 Vivaldi, C. HER2 overexpression as a poor prognostic determinant in resected biliary tract cancer. Oncologist. 2020;25(10):886-893. doi:10.1634/theoncologist.2019-0922.13 Weisser NE, Sanches M, Escobar-Cabrera E et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nature Communications . 2023 Mar 13;14(1):1394. doi: 10.1038/s41467-023-37029-314 U.S. Food and Drug Administration . Ziihera® (zanidatamab-hrii) prescribing information. Accessdata.fda.gov. Updated November 2024 . Accessed April 22, 2025 . https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761416s000lbl.pdf15 Meric-Bernstam, F., Beeram, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. The Lancet Oncology. 2022; doi: 10.1016/S1470-2045(22)00621-016 Jazz Pharmaceuticals, Inc , Data on file. View original content to download multimedia:https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-receives-chmp-positive-opinion-for-zanidatamab-for-the-treatment-of-advanced-her2-positive-biliary-tract-cancer-302438480.html SOURCE Jazz Pharmaceuticals plc

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 For U.S. media and investors only 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). 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). 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. "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. "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." 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. 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 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. More information about Ziihera, the Full Prescribing Information, including Boxed Warning and Patient Information, is available here. 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). 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1 Zanidatamab is not approved anywhere else in the world. 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. 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). 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. WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity ZIIHERA 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. 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. Left Ventricular Dysfunction ZIIHERA 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). LVD resolved in 70% of patients. 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. The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%. Infusion-Related Reactions ZIIHERA 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. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day. 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. 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. Diarrhea ZIIHERA can cause severe diarrhea. 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. ADVERSE REACTIONS Serious 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%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA. 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%). USE IN SPECIFIC POPULATIONS Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients. Geriatric Use Of 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. No overall differences in safety or efficacy were observed between these patients and younger adult patients. About Biliary Tract Cancer BTC, 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. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.4,5,6,7 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. 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 Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit for more information. Contacts: Jazz Media Contact: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Jazz Investor Contact: Jeff Macdonald Executive Director, Investor Relations Jazz Pharmaceuticals plc [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 SOURCE Jazz Pharmaceuticals plc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Ziihera is the first and only dual HER2-targeted bispecific antibody approved for HER2+ BTC in the U.S. Ziihera received accelerated approval based on results including a 52% objective response rate and median duration of response of 14.9 months as determined by independent central review (ICR) from the HERIZON-BTC-01 clinical trial Company to host investor webcast on Dec. 11, 2024 DUBLIN, Ireland I November 20, 2024 I 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). 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. “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. 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.” 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. 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 “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. “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.” “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. 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.” 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 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 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%). 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 . 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. 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. 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. About the Phase 2b HERIZON-BTC-01 Trial The 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. 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+. 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. Investor Webcast on Wednesday, December 11, 2024 The 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. 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 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. An archive of the webcast will be available for at least one week following the presentation on the Investors section of the company’s website at www.jazzpharmaceuticals.com . More information about Ziihera , the Full Prescribing Information, including Boxed Warning and Patient Information, is available here . 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). 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 1 Zanidatamab is not approved anywhere else in the world. 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. 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 European Medicines Agency for the treatment of BTC and gastric cancer. WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity ZIIHERA 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. 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. Left Ventricular Dysfunction ZIIHERA 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). LVD resolved in 70% of patients. 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. The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%. Infusion-Related Reactions ZIIHERA 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. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day. 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. 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. Diarrhea ZIIHERA can cause severe diarrhea. 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. ADVERSE REACTIONS Serious 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%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA. 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%). USE IN SPECIFIC POPULATIONS Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients. Geriatric Use Of 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. No overall differences in safety or efficacy were observed between these patients and younger adult patients. About Biliary Tract Cancer BTC, 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. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually. 4,5,6,7 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. 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 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. References: 1 ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2 Valle JW, et al. Lancet 2021; 397:428-44 3 Siegel RL, et al. CA Cancer J Clin 2022; 72;7-33 4 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. et al. Cancer Metastasis Rev 36, 141–157 (2017), Nobuyoshi Hiraoka, et al. Human Pathology, Volume 105, 2020, Pages 9-19 7 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 SOURCE: Jazz Pharmaceuticals