Jazz Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ziihera® (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) 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 and only dual HER2-targeted bispecific antibody approved for this indication in the U.S.
The FDA's decision was based on data from the HERIZON-BTC-01 trial, a Phase 2b study that evaluated zanidatamab as a single agent in patients with HER2-positive BTC who had received prior gemcitabine-containing therapy. The trial demonstrated a 52% objective response rate (ORR) with a 95% confidence interval of 39% to 65%, and a Kaplan-Meier estimated median duration of response (DOR) of 14.9 months with a 95% confidence interval of 7.4 months to not estimable, as determined by independent central review (ICR).
Clinical Impact and Expert Commentary
"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."
Dr. James Harding, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center, commented, "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."
Ongoing Confirmatory Trial
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 trial is currently underway 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.
Safety Profile
The safety profile of Ziihera was evaluated in 80 patients in the HERIZON-BTC-01 trial. Serious adverse reactions occurred in 53% of patients. The most common adverse reactions (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue. A boxed warning for embryo-fetal toxicity is included in the prescribing information, advising patients of the risk and need for effective contraception.
About Zanidatamab
Zanidatamab is a bispecific HER2-directed antibody that binds to two distinct extracellular domains of HER2, leading to receptor internalization, reduced tumor cell surface HER2, and tumor growth inhibition through mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).
Biliary Tract Cancer (BTC) Overview
Biliary tract cancers, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for less than 1% of all adult cancers globally and are often associated with a poor prognosis. HER2 is a validated target for antitumor therapy, and approximately 12,000 people are diagnosed with HER2+ BTC annually across the U.S., Europe, and Japan.
