The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Ziihera (zanidatamab) for the treatment of adult patients with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC). This approval, announced by Zymeworks and Jazz Pharmaceuticals, marks a significant advancement in the treatment landscape for this aggressive cancer. Ziihera is administered intravenously and is indicated for patients whose HER2-positive status has been confirmed by an FDA-approved test.
The accelerated approval was based on promising data demonstrating a 52% objective response rate (ORR) and a median duration of response (DoR) of 14.9 months, as determined by independent central review. These results highlight the potential of Ziihera as a targeted therapy in a setting where treatment options are limited. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Clinical Efficacy and Safety
Ziihera's efficacy was evaluated in a clinical trial involving patients with HER2-positive BTC who had previously received treatment. The trial's primary endpoint was ORR, with DoR as a key secondary endpoint. The observed ORR of 52% signifies a clinically meaningful response in a patient population with a high unmet need. The median DoR of 14.9 months suggests a durable benefit for responding patients.
Mechanism of Action
Ziihera (zanidatamab) is a bispecific antibody that simultaneously binds to two distinct epitopes of the HER2 receptor. This dual targeting mechanism leads to HER2 receptor clustering, internalization, and degradation, ultimately inhibiting HER2 signaling and promoting tumor cell death. The bispecific design offers a unique approach to HER2 targeting, potentially overcoming resistance mechanisms associated with traditional HER2 inhibitors.
Commercial Implications
Under the terms of the license and collaboration agreement with Jazz Pharmaceuticals, Zymeworks has earned a milestone payment of $25 million based on the FDA approval. Furthermore, Zymeworks is eligible to receive up to an additional $500 million in regulatory milestone payments and $862.5 million in commercial milestone payments, along with tiered royalties ranging from 10% to 20% of net sales by Jazz. This collaboration leverages Jazz’s global commercial infrastructure to facilitate the rapid advancement of zanidatamab in multiple tumor types.
Addressing Unmet Needs in Biliary Tract Cancer
Biliary tract cancer is a rare and aggressive malignancy with limited treatment options, particularly in the advanced stages. The approval of Ziihera represents a significant step forward, providing a new chemotherapy-free option for patients with HER2-positive disease. This approval underscores the importance of HER2 testing in BTC to identify patients who may benefit from this targeted therapy.
