Ziihera (Zanidatamab-hrii) Approved for HER2-Positive Biliary Tract Cancer
Key Insights
The FDA granted accelerated approval to Ziihera (zanidatamab-hrii (search)) for treating HER2 (search)-positive biliary tract cancer (search) (BTC) in previously treated adults.
Ziihera is the first chemotherapy-free, dual HER2 (search)-targeted bispecific antibody approved for BTC, offering a new treatment option.
Approval was based on the HERIZON-BTC-01 trial, which demonstrated a 52% objective response rate and a 14.9-month median duration of response.
Jazz Pharmaceuticals' Ziihera (zanidatamab-hrii (search)) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with previously treated, unresectable or metastatic HER2 (search)-positive (IHC 3+) biliary tract cancer (search) (BTC). This approval marks a significant advancement in the treatment landscape for BTC, providing the first chemotherapy-free, dual HER2-targeted bispecific antibody for this indication.
The approval was based on data from the HERIZON-BTC-01 trial, a Phase 2b clinical trial that evaluated zanidatamab as a single agent in patients with previously treated HER2 (search)-positive BTC. The trial met its primary endpoint, demonstrating a confirmed objective response rate (cORR) of 52% as assessed by independent central review (ICR). The median duration of response (DOR) was 14.9 months.
Mechanism of Action
Ziihera (zanidatamab-hrii (search)) is a bispecific HER2 (search)-directed antibody that binds to two distinct extracellular domains of the HER2 receptor. This dual binding results in receptor internalization and downregulation, inhibiting tumor growth and inducing cell death through complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).
Clinical Trial Data
The HERIZON-BTC-01 trial, supporting the accelerated approval, enrolled patients with HER2 (search)-positive BTC who had progressed on prior therapies. The objective response rate of 52% and the median duration of response of 14.9 months highlight the clinical benefit of zanidatamab in this patient population. Serious adverse reactions occurred in 53% of patients, with common adverse reactions (≥20%) including diarrhea (50%), infusion-related reactions (35%), abdominal pain (29%), and fatigue (24%).
Safety Profile and Warnings
The prescribing information for Ziihera includes a boxed warning for embryo-fetal toxicity, advising females of reproductive potential to use effective contraception during treatment and for 4 months following the last dose. Other warnings and precautions include left ventricular dysfunction, infusion-related reactions, and diarrhea. Regular monitoring of left ventricular ejection fraction (LVEF) is recommended, and premedications should be administered to prevent infusion-related reactions.
Ongoing and Future Studies
While the current approval is based on overall response rate and duration of response, continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. Jazz Pharmaceuticals is currently evaluating zanidatamab in the Phase 3 HERIZON-BTC-302 trial in combination with standard therapy for first-line HER2 (search)-positive BTC. Zanidatamab is also being investigated in other HER2-expressing cancers, including gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC).
Investor Webcast
Jazz Pharmaceuticals will host a webcast on Wednesday, December 11, 2024, at 4:30 p.m. ET / 9:30 p.m. GMT to provide an overview of clinical data, patient need, and commercialization strategy for Ziihera. Dr. Shubham Pant from The University of Texas MD Anderson Cancer Center will discuss previously disclosed BTC data from the HERIZON-BTC-01 trial during the webcast.