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At its April 2025 meeting, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a conditional marketing authorization for Ziihera (zanidatamab, Jazz Pharmaceuticals Ireland Limited) for the treatment of adults with unresectable, locally advanced, or metastatic human epidermal growth factor receptor 2 (HER2)–positive biliary tract cancer.

A conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required.

The decision by the CHMP was based on the findings of the HERIZON-BTC-01 study, a global, multicenter, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy. Patients were assigned into cohorts on the basis of HER2 immunohistochemistry (IHC) score — cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+) — and received zanidatamab 20 mg/kg intravenously every 2 weeks. The median duration of follow-up was 12.4 months.

The researchers said that 33 out of 80 (41.3%) patients in cohort 1 demonstrated “objective responses” with meaningful clinical benefit and with a manageable safety profile.

In granting the authorization, the CHMP said that the benefits of Ziihera were its confirmed objective response rate and duration of response in patients with HER2-positive unresectable, locally advanced, or metastatic biliary tract cancer who had previously received chemotherapy.

Meaningful Clinical Benefit

The active substance of Ziihera, zanidatamab, is a HER2 inhibitor.

HER2 is a protein found at very high levels on the surface of some types of cancer cells and sends signals to the cell that can promote the growth and/or spread of cancer.

Zanidatamab is a bispecific (dual-targeting) monoclonal antibody that can recognize and simultaneously bind two separate sites on HER2: Extracellular domains 2 and 4 on separate HER2 monomers. Binding of zanidatamab with HER2 results in internalization, leading to a reduction of HER2 on the cell surface. Zanidatamab induces complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, resulting in tumor growth inhibition and tumor cell death.

The full indication for Ziihera, which will be available as a 300-mg powder for concentrate for solution for infusion as monotherapy, is for the treatment of adults with unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (previously treated with at least one prior line of systemic therapy).

The most common side effects include diarrhea, infusion-related reactions, fatigue, anemia, and rash.

Ziihera was designated as an orphan medicine during its development for use against a rare, life-threatening, or chronically debilitating condition or, for economic reasons, would have been unlikely to have been developed without incentives. The EMA said that it would now review the information available to date to determine if the orphan designation can be maintained.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.