FDA Accelerates Approval of Zanidatamab for HER2-Positive Bile Duct Cancer

Jazz Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) has approved Zanidatamab, a bi-specific antibody drug developed in collaboration with Zymeworks for the HER2 target. The drug, marketed under the trade name Ziihera, was approved for the treatment of previously treated, unresectable, locally advanced or metastatic HER2-positive biliary tract cancer.

The official press release notes that Zenidatumab becomes the first and currently only FDA-approved HER2 bisspecific antibody drug specifically for HER2-positive biliary tract cancer.

Zenidatumab (ZW25) is a bispecial antibody based on Zymeworks' Azymetric platform that binds two different HER2 epitopes simultaneously to achieve dual complementary site binding. This unique structural design enables Zenidatumab to perform multiple mechanisms of action, including double blocking of HER2 signaling, enhancing the antibody's ability to bind to HER2 protein and effectively clearing HER2 protein from the cell surface, as well as enhancing anti-tumor activity in patients through powerful antibody effector function.

Previously, Zenidumab has been granted breakthrough therapy designation, fast track status, priority review status and orphan drug status by the FDA, and has also been granted breakthrough therapy and priority review status by the National Drug Administration of China (NMPA).

Zenidatumab was originally developed by Zymeworks. In 2018, Beigene entered into a $430 million partnership agreement with Zymeworks to acquire exclusive rights to the drug and its other bispecial antibody drug, ADC, in Asia (excluding Japan), Australia and New Zealand. In October 2022, Jazz signed a $1.76 billion partnership agreement with Zymeworks, giving it rights to Zenidumab in the United States, Europe, Canada, Japan and other regions.

At present, the National Medical Products Administration (NMPA) has accepted the marketing application of Zenidumab for the second-line treatment of HER2-positive biliary cancer (CXSS2400056) and included it in the priority review process, which is expected to be approved in the second quarter of next year.

The U.S. approval of Zenidumab is based on data from the Phase II b trial HERIZON-BTC-01. In Cohort 1 of the trial, a total of 62 patients with HER2-positive biliary tract cancer were evaluated for Zenidatumab, with the primary outcome measures being objective response rate (ORR) and duration of response (DOR) as determined by RECISTv1.1.1 criteria. The results showed an ORR of 52% and a median duration of response of 14.9 months.