Jazz’s Ziihera gets FDA approval for advanced biliary tract cancer

Jazz Pharmaceuticals has recently received accelerated approval from the FDA for its bispecific antibody, Ziihera (zanidatamab-hrii), aimed at treating adults with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC). This approval marks Ziihera as the first and only dual HER2-targeted therapy approved for this condition in the United States.

Patients with unresectable or metastatic HER2-positive BTC have historically faced a significant unmet need, with limited treatment options available. Rob Iannone, the chief medical officer at Jazz, highlighted that Ziihera provides a crucial chemotherapy-free treatment option for these patients.

The approval of Ziihera is based on promising data from the Phase IIb HERIZON-BTC-01 study. This trial demonstrated a 52% objective response rate, with a median duration of response of 14.9 months among a cohort of 62 patients with HER2-positive BTC. Despite 53% of participants experiencing serious adverse reactions, the rate of permanent treatment-related discontinuations was relatively low, at 2.5%. The drug's label includes a boxed warning about the risk of embryo-fetal harm if used during pregnancy.

Full approval of Ziihera is dependent on further results from the ongoing Phase III HERIZON-BTC-302 confirmatory study. This trial is evaluating Ziihera in combination with standard therapies for HER2-positive BTC in the front-line setting.

In the advanced BTC treatment landscape, Ziihera is expected to compete with AstraZeneca’s Imfinzi (durvalumab) and Merck & Co.’s Keytruda (pembrolizumab), both of which were approved by the FDA in recent years in combination with chemotherapy.

Jazz Pharmaceuticals acquired the rights to Ziihera from Zymeworks for key markets including the United States, Europe, and Japan in 2022. BeiGene holds the rights to the drug in certain Asia-Pacific regions. Jazz is also conducting late-stage studies of Ziihera in other HER2-positive solid tumors.

One such study, the HERIZON-GEA-01 trial, is investigating Ziihera combined with chemotherapy, with or without BeiGene’s Tevimbra (tislelizumab), in front-line advanced or metastatic gastroesophageal adenocarcinomas. Another trial, the EmpowHER-303 study, is exploring the use of Ziihera in combination with chemotherapy for patients with metastatic breast cancer who have either progressed on or are intolerant to AstraZeneca and Daiichi’s Enhertu (trastuzumab deruxtecan).