US FDA Approves Jazz Pharma’s Ziihera to Treat Adults with Biliary Tract Cancer

US FDA Approves Jazz Pharma’s Ziihera to Treat Adults with Biliary Tract Cancer

By, Admin 22 November 2024

US FDA approves Jazz Pharma’s Ziihera to treat adults with previously treated, unresectable or metastatic HER2-positive biliary tract cancer

Overview

Jazz Pharmaceuticals plc announced the US 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. 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. 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.

Words from the CMO: Jazz Pharmaceuticals

  • 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 tumours, with the goal of improving outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers.

Data Behind the FDA Approval

  • 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 programme. 
  • Longer follow-up data showing improvement upon previously reported DOR were reported at the ASCO Annual Meeting 2024.

From the Memorial Sloan Kettering Cancer Center

  • 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.

Words from the CEO: Cholangiocarcinoma Foundation

  • 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.

Study for Ziihera Efficacy

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 Tumours) 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.

The 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 tumour 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+. 
  • Tumours 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.

About the Antibody: Ziihera

  • 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 tumour cell surface. 
  • Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). 
  • These mechanisms result in tumour growth inhibition and cell death in vitro and in vivo. 
  • 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. 
  • The US 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).
  • Zanidatamab is not approved anywhere else in the world.

Zanidatamab: fro Solid Tumors

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

The BTA for Zanidatamab

  • 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 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. 
  • The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. 
  • Across the US, Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.

About the Company: Jazz Pharmaceuticals

  • Jazz Pharmaceuticals plc is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. 
  • The company dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options.

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