EC Approves Jazz Pharmaceuticals' Ziihera for Advanced Biliary Tract Cancer

The European Commission (EC) has conditionally approved Jazz Pharmaceuticals' Ziihera (zanidatamab) for the treatment of certain patients with advanced biliary tract cancer (BTC). This decision marks a significant development in the management of BTC, targeting patients with HER2-positive (IHC 3+) tumors who have already undergone at least one systematic treatment.

Ziihera is a bispecific antibody designed to target the human epidermal growth factor receptor 2 (HER2). It has been approved for use as a standalone treatment in adults with locally advanced, unresectable, or metastatic HER2-positive BTC. The decision by the EC was heavily influenced by data from the phase 2b HERIZON-BTC-01 clinical trial, which involved a group of 80 patients with confirmed HER2-positive BTC.

The HERIZON-BTC-01 trial aimed to evaluate the efficacy of Ziihera through its primary endpoint, the confirmed objective response rate (cORR). In this trial, Ziihera achieved a cORR of 41.3%, including two complete responses at a median follow-up period of 21.9 months. Further results showed that the median duration of response (DoR) for Ziihera was 14.9 months, and the median overall survival (OS) was recorded at 15.5 months.

A detailed analysis focusing on a subgroup of 62 patients with IHC 3+ tumors revealed even more promising results. In this subgroup, Ziihera achieved a cORR of 51.6%, maintaining a median DoR of 14.9 months, and the median OS improved to 18.1 months. This data underscores the potential efficacy of Ziihera in treating this patient population.

BTCs, which include gallbladder cancer and cholangiocarcinoma, are rare and notably aggressive forms of cancer. They are often diagnosed at stages where surgical intervention is not feasible. Globally, around 26% of BTC cases are HER2-positive, a factor associated with less favorable outcomes compared to those with HER2-negative disease.

Robert Iannone, who holds key leadership roles at Jazz Pharmaceuticals, emphasized the importance of this conditional approval. According to Iannone, the approval signifies considerable progress in addressing the needs of patients battling advanced HER2-positive BTC. He noted that Ziihera is the first treatment targeting HER2 that has been specifically authorized for use in the European Union for this patient group. He also highlighted that the EC's decision reflects both the robust data from the HERIZON-BTC-01 trial and the pressing need for new innovations in the treatment of rare gastrointestinal cancers.

However, the conditional nature of the approval means that continued authorization of Ziihera will depend on further evidence from ongoing research. Specifically, the phase 3 HERIZON-BTC-302 trial is designed to confirm the clinical benefits of Ziihera. This trial is evaluating the effectiveness of the drug when used in combination with standard-of-care therapy for patients with HER2-positive BTC in a first-line treatment setting. The outcomes of this ongoing trial will determine the future availability of Ziihera for this indication.