Ziihera Approved By U.S. FDA For Treating HER2-Positive Biliary Tract Cancer

Jazz Pharmaceuticals plc has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Ziihera® (zanidatamab-hrii) 50mg/mL, an intravenous treatment for adults with previously treated, unresectable, or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), confirmed using an FDA-approved diagnostic test. Continued approval may depend on the outcome of a confirmatory trial.

Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, said in a statement,

"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." 

He also said, "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, intending to improve outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers."

The Phase 3 HERIZON-BTC-302 trial evaluates zanidatamab (Ziihera®) with standard-of-care therapy as a first-line treatment for HER2-positive biliary tract cancer (BTC). Ziihera’s FDA approval is based on Phase 2b HERIZON-BTC-01 data, which reported a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months in 62 patients. Safety data from 80 patients showed severe adverse reactions in 53%, with common side effects including diarrhoea and fatigue.

The trial met 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. More extended follow-up data showing improvement upon previously reported DOR were reported at the ASCO Annual Meeting 2024

Dr James Harding, associate attending Gastrointestinal Oncology and Early Drug Development Services at Memorial Sloan Kettering Cancer Center, commented, "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. 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."

Zanidatamab is also under investigation in other cancers, including HER2-positive gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC), with multiple Phase 3 trials in process. Ziihera has a boxed warning for embryo-fetal toxicity, advising effective contraception for patients.

Stacie Lindsey, CEO and founder of the Cholangiocarcinoma Foundation said, "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. 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."