Regulatory Decision Summary for Ziihera

The purpose of this New Drug Submission (NDS) was to obtain market authorization under the Notice of Compliance with conditions (NOC/c) pathway for Ziihera (zanidatamab), a bispecific HER2-directed antibody, for the treatment of adults with previously treated, unresectable locally advanced or metastatic HER2-positive biliary tract cancer (BTC).

After review, the indication recommended for authorization under the NOC/c pathway is:

Ziihera (zanidatamab) is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as monotherapy.

Marketing authorization with conditions was based on objective response rate (ORR) and duration of response (DOR). An improvement in survival has not yet been established.

The recommendation for authorization of Ziihera was based on the results of HERIZON-BTC-01, an open label, single arm trial in 62 adult patients with unresectable locally advanced or metastatic HER2-positive (immunohistochemistry (IHC) 3+) BTC who had disease progression or were intolerable to prior gemcitabine-based systemic chemotherapy. Patients received 20 mg/kg of Ziihera administered as an intravenous infusion once every 2 weeks until disease progression or unacceptable toxicity.

The primary efficacy endpoint was the confirmed objective response rate (cORR) determined by independent central review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. The reported cORR was 51.6% and the median duration of response was 14.9 months. An improvement in survival has not yet been established. A survival benefit will be evaluated in a controlled randomized Phase 3 clinical trial which is required as a condition of authorization.

The safety of Ziihera was evaluated in 87 patients with unresectable locally advanced or metastatic BTC in study HERIZON-BTC-01. The most common adverse reactions (≥ 20%) included diarrhea, infusion-related reaction, abdominal pain, anemia, fatigue, alanine aminotransferase increased and aspartate aminotransferase increased. Important identified risks included embryo-fetal toxicity, left ventricular dysfunction, infusion-related reactions, and pneumonitis. The safety findings and risk mitigation and risk management measures are described in the Ziihera Product Monograph.

The benefit-risk profile of Ziihera is considered favourable when used under the conditions of use recommended in the Product Monograph. Therefore, a Notice of Compliance with conditions (NOC/c) was recommended.

For further details about Ziihera treatment, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.