The Food and Drug Administration has approved Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC).
Ziihera, the first dual HER2-targeted bispecific antibody approved for this patient population in the United States, received accelerated approval based on a 52% objective response rate (ORR) and a median duration of response of 14.9 months in the phase 2b HERIZON-BTC-01 clinical trial, according to a news release from manufacturer Jazz Pharmaceuticals.
The accelerated approval of Ziihera at 50 milligrams per milliliter for injection for intravenous use may be contingent upon verification in a confirmatory trial, with phase 3 HERIZON-BTC-302 confirmatory trial currently ongoing, according to the news release.
Glossary
Unresectable: tumors that cannot be surgically removed.
Intravenous: treatment given through the vein.
Metastatic: cancer that has spread from where it started.
Objective response rate (ORR): patients who responded partially or completely to treatment.
Breakthrough therapy designation: a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint, according to the FDA’s website.
Boxed Warning: known as a “black box” warning, is the most serious warning the FDA can issue for a drug.
"BTC is a devastating disease with a poor prognosis and five-year survival rates under 5% 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 Dr. Rob Iannone, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, in the news release. "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 [Ziihera] 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."
Results from HERIZON-BTC-01 were previously reported at the American Society of Clinical Oncology Annual Meetings in 2023 and 2024 and published in The Lancet Oncology. According to the news release, the drug’s efficacy was evaluated among 62 patients with HER2-positive BTC.
The drug comes with a Boxed Warning for embryo-fetal toxicity, noting that exposure to the drug during pregnancy can cause embryo-fetal harm. The safety profile of Ziihera was demonstrated among 80 patients in HERIZON-BTC-01, with serious side effects occurring in 53% of patients. The most common side effects occurring in at least 20% of patients were diarrhea, infusion-related reaction, abdominal pain and fatigue. Serious side effects among more than 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%). One patient experienced a fatal side effect of hepatic (liver) failure, and patient discontinuation due to side effects occurred in 2.5% of patients.
"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, in the news release. "[Ziihera] 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 in the news release. "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."
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