China's National Medical Products Administration (NMPA) has granted conditional approval to zanidatamab for the treatment of patients with previously treated, unresectable or metastatic HER2-positive biliary tract cancer, making it the first and only dual HER2-targeted bispecific antibody approved for HER2-high expression (IHC3+) biliary tract cancer in China. The approval was obtained by Zymeworks' collaboration partner, BeOne Medicines Ltd., under the terms of its Asia Pacific license and collaboration agreement with Zymeworks.
Addressing Critical Unmet Medical Need
"Zanidatamab's conditional approval in China is a meaningful advancement for patients living with HER2-positive BTC, a population with historically high unmet need and poor prognoses," said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. The approval represents a significant milestone for patients with biliary tract cancer, which accounts for approximately 3% of all digestive system tumors and is often associated with poor prognosis.
Biliary tract cancers, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, affect approximately 11%-25.2% of patients who are HER2-positive. The incidence rate of biliary tract cancer is rising globally, particularly in Asian countries and regions, making this approval especially relevant for the Chinese patient population.
Financial Impact and Partnership Terms
The NMPA approval triggers a $20 million milestone payment to Zymeworks from BeOne Medicines. Under the terms of their agreement, Zymeworks has already received $61 million in upfront and milestone payments, as well as certain co-development funding for zanidatamab clinical studies. The company remains eligible to receive up to $144 million in additional development and commercial milestones and tiered royalties of up to 19.5% of net sales in BeOne Medicine's territories.
Mechanism of Action and Clinical Foundation
Zanidatamab is a dual HER2-targeted bispecific antibody that simultaneously binds extracellular domains 2 and 4 on separate HER2 monomers (binding in trans). Binding of zanidatamab with HER2 results in internalization leading to a reduction of the receptor on the cell surface. The drug induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), mechanisms that result in tumor growth inhibition and tumor cell death.
The conditional approval is based on results from the HERIZON-BTC-01 clinical study. Continued approval of this indication will depend on the verification of clinical benefit in the patient population through ongoing confirmatory trials.
Global Regulatory Progress
This approval follows a series of regulatory successes for zanidatamab. The U.S. Food and Drug Administration granted accelerated approval in November 2024 for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. In April 2025, the European Medicines Agency Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of zanidatamab for the treatment of advanced HER2-positive biliary tract cancer.
Broader Development Pipeline
Zanidatamab is currently under regulatory review in the EU for second-line biliary tract cancer and is being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with multiple HER2-expressing cancers. Zymeworks is also rapidly advancing a robust pipeline of wholly-owned product candidates, with Phase 1 studies for ZW171 and ZW191 actively recruiting and an investigational new drug application for ZW251 planned for mid-2025.
