The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ziihera (zanidatamab-hrii) for the treatment of adult patients with previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC). This approval marks a significant advancement in the treatment landscape for BTC, a disease with historically poor prognosis and limited therapeutic options. Ziihera is the first dual HER2-targeted bispecific antibody approved for this patient population.
The accelerated approval was based on data from the phase 2b HERIZON-BTC-01 clinical trial, which demonstrated a 52% objective response rate (ORR) and a median duration of response of 14.9 months among patients treated with Ziihera. These findings were presented at the American Society of Clinical Oncology (ASCO) Annual Meetings in 2023 and 2024 and published in The Lancet Oncology.
Clinical Efficacy and Safety
The HERIZON-BTC-01 trial evaluated the efficacy of Ziihera in 62 patients with HER2-positive BTC. The results showed promising antitumor activity, leading to the FDA's accelerated approval. However, the approval is contingent upon verification of clinical benefit in a confirmatory trial, the ongoing phase 3 HERIZON-BTC-302 trial.
The safety profile of Ziihera was assessed in 80 patients in the HERIZON-BTC-01 trial. Serious side effects occurred in 53% of patients, with the most common adverse reactions (≥20%) being diarrhea, infusion-related reactions, abdominal pain, and fatigue. Notable serious side effects included biliary obstruction (15%), biliary tract infection (8%), and sepsis (8%). The drug carries a Boxed Warning for embryo-fetal toxicity, advising caution in pregnant women.
Expert Commentary
"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. "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."
Dr. James Harding, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center, added, "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. Ziihera has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer."
Impact on the BTC Community
The approval of Ziihera represents a significant milestone for patients with HER2-positive BTC, offering a new treatment option that has demonstrated promising efficacy in clinical trials. The Cholangiocarcinoma Foundation also welcomes this approval, highlighting the potential for improved quality of life and extended time for patients and their families.
