FDA Sets Date for Zanidatamab in Bile Duct Cancer

The FDA has granted priority review of Jazz Pharmaceuticals’ biologics license application (BLA) for zanidatamab to treat patients with unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Nov. 29, 2024. 

Biliary tract cancer is a group of rare and aggressive cancers. It develops in the bile ducts, from the liver to the small intestine. About 8,000 people are diagnosed each year with bile tract cancers, according to the American Cancer Society. The five-year survival rate for metastatic biliary tract cancer is less than 5%, highlighting an urgent need for new treatments. Research has shown that HER2 is involved in biliary tract cancers. HER2 is a protein located in cells that plays a role in tumor growth.

“The priority review designation for zanidatamab underscores the critical need for new treatment options for patients with locally advanced or metastatic HER2-positive BTC, a devastating disease with a poor prognosis,” Rob Iannone, M.D., executive vice president, global head of research and development of Jazz Pharmaceuticals, said in a news release. “Upon approval, zanidatamab will be the first HER2-targeted treatment specifically indicated for these patients.”

Zanidatamab is bispecific antibody that targets the human epidermal growth factor receptor 2 (HER2). Zanidatamab binds to two non-overlapping epitopes of the HER2 receptor, which blocks HER2 signaling and removes the HER2 protein from the cell surface. Zanidatamab is being developed by Jazz and BeiGene, under license agreements from Zymeworks, which first developed the molecule.

Jazz’s submission is based on results from Cohort 1 of the phase 2b HERIZON-BTC-01 clinical. The trial demonstrated a primary endpoint of 41.3% confirmed objective response rate (cORR) with a median duration of response (DOR) of 12.9 months at a median follow-up of 12.4 months. Among the 33 responders, 49% had ongoing responses and 82% had a response lasting more than 16 weeks.

Results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023, published in The Lancet Oncology. Overall survival, updated duration of response and additional long-term follow-up data from the phase 2b HERIZON-BTC-01 trial will be presented at the upcoming ASCO Annual Meeting 2024.

The phase 3 trial HERIZON-BTC-302 to evaluate the efficacy and safety of zanidatamab in combination with standard-of-care therapy against standard-of-care therapy alone to treat HER2-positive biliary tract cancer is ongoing. Jazz officials said HERIZON-BTC-302 is expected to serve as the confirmatory trial for zanidatamab.