FDA Fast-Tracks Zanidatamab for HER2-Positive Bile Duct Cancer Approval

Jazz Pharmaceuticals has recently announced that the U.S. Food and Drug Administration (FDA) has granted approval for Zanidatamab, a bi-specific antibody drug developed in partnership with Zymeworks. Known commercially as Ziihera, this medication is now approved for treating patients with previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer.

The press release highlights that Zanidatamab stands out as the first and only FDA-approved bi-specific antibody drug specifically targeting HER2-positive biliary tract cancer. This approval marks a significant milestone in the treatment of this aggressive cancer type.

Zanidatamab, also referred to as ZW25, is engineered using Zymeworks' Azymetric platform. This platform allows the antibody to bind simultaneously to two distinct HER2 epitopes, providing dual side binding. The innovative structural design of Zanidatamab allows it to enact multiple mechanisms that include blocking HER2 signaling pathways, enhancing binding affinity to HER2 proteins, and effectively clearing these proteins from the cell surface. Additionally, the drug amplifies anti-tumor activity in patients through potent antibody effector functions.

Prior to this approval, Zanidatamab had already received multiple designations from the FDA, including breakthrough therapy designation, fast track status, priority review status, and orphan drug status. Additionally, it also earned breakthrough therapy and priority review status from China's National Drug Administration (NMPA).

The origins of Zanidatamab trace back to Zymeworks. In 2018, Zymeworks entered into a $430 million partnership with Beigene to secure exclusive rights to this drug and other bi-specific antibody drugs in regions such as Asia (excluding Japan), Australia, and New Zealand. Later, in October 2022, Jazz Pharmaceuticals signed a $1.76 billion agreement with Zymeworks, gaining rights to Zanidatamab in the United States, Europe, Canada, Japan, and several other territories.

Currently, the National Medical Products Administration (NMPA) of China has accepted the marketing application for Zanidatamab for the second-line treatment of HER2-positive biliary cancer and is reviewing it on a priority basis. Approval is anticipated by the second quarter of next year.

The FDA's approval of Zanidatamab is grounded in data from the Phase IIb HERIZON-BTC-01 trial. This trial involved 62 patients with HER2-positive biliary tract cancer. The primary endpoints evaluated were objective response rate (ORR) and duration of response (DOR), as per RECISTv1.1 criteria. Results from the trial indicated an ORR of 52% and a median response duration of 14.9 months.

This recent approval by the FDA offers new hope for patients battling HER2-positive biliary tract cancer, providing them with an innovative treatment option.