Jazz Pharmaceuticals Breaks Ground on Ziihera® for Treatment of HER2-Positive Biliary Tract Cancer
Jazz Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Ziihera® (zanidatamab-hrii) 50mg/mL for intravenous use. The treatment is intended for adults with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC), identified through an FDA-approved diagnostic test.
The approval is based on data from the HERIZON-BTC-01 trial, which reported a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months, as assessed by independent central review (ICR).
The FDA's decision is provisional and subject to confirmation of clinical benefits in an ongoing Phase 3 confirmatory trial, HERIZON-BTC-302. This trial compares zanidatamab in combination with standard-of-care therapies against standard-of-care therapies alone for first-line treatment of HER2-positive BTC.
BTC is a severe condition with low survival rates, especially in metastatic stages, where the five-year survival rate is below five percent. HER2-positive BTC has been particularly challenging to treat due to limited therapeutic options. Ziihera provides the first dual HER2-targeted bispecific antibody therapy without chemotherapy, addressing a critical need in this patient group.
Ziihera’s safety profile was evaluated in 80 patients during the HERIZON-BTC-01 trial. Serious adverse reactions occurred in 53% of patients, including biliary obstruction, biliary tract infection, sepsis, and pneumonia. A fatal case of hepatic failure was also reported. Common side effects included diarrhoea, infusion-related reactions, abdominal pain, and fatigue. Permanent discontinuation due to adverse reactions occurred in 2.5% of patients. A boxed warning highlights the potential for embryo-fetal toxicity, advising effective contraception for patients during treatment.
The Phase 3 HERIZON-BTC-302 trial is currently underway to verify the clinical benefits of Ziihera. This global study is examining the efficacy of zanidatamab combined with standard-of-care therapies in comparison to standard-of-care therapies alone for first-line treatment of HER2-positive BTC. Continued approval for Ziihera is contingent upon the results of this trial.
In addition to BTC, zanidatamab is being studied for its potential in treating other HER2-expressing tumours. These include advanced gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC). Ongoing Phase 3 trials include HERIZON-GEA-01, evaluating zanidatamab with chemotherapy, with or without tislelizumab, for HER2-positive GEAs, and EmpowHER-303, investigating zanidatamab with chemotherapy for HER2-positive mBC patients who have progressed on or are intolerant to trastuzumab deruxtecan.
