FDA Approves Biliary Tract Cancer Antibody Treatment

bile duct cancer © samunella - stock.adobe.com

Jazz Pharmaceuticals announced the recent FDA accelerated approval of Ziihera (zanidatamab-hrii) for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. This approval makes Ziihera the first and only dual HER2-targeted bispecific antibody treatment for this indication. An investor webcast will be held on Dec. 11 at 4:30 p.m. EST to discuss further details, according to a news release.

Potential Ziihera patients may have their cancer identified using the PATHWAY HER2 (4B5) test, now approved under an FDA label expansion. This test, approved on Nov. 25, is the first and only FDA-approved companion diagnostic for HER2-positive biliary tract cancer.

Ziihera is produced in Chinese hamster ovary cells via recombinant DNA technology, official prescribing information states. These cells are chosen because they can produce complex proteins similar to human cells. More than 70% of all recombinant antibodies have been produced from Chinese hamster ovaries since 2016, a study published in Critical Reviews in Biotechnology adds.

Biliary tract cancer affects bile ducts within the gallbladder, liver and small intestine. The cancer becomes HER2-positive when the tumor cells overexpress the HER2 protein, which causes the tumors to grow rapidly. When it becomes metastatic, the five-year survival rate is less than 5%.

The recommended dose of Ziihera is 20 mg/kg given as an intravenous infusion every two weeks. It’s also recommended that patients be given acetaminophen, an antihistamine and a corticosteroid 30 to 60 minutes before treatment to avoid infusion-related reactions. Ziihera comes as a powder that must be reconstituted and diluted with sterile water before use.

This approval is based on the results of the phase 2b HERIZON-BTC-01 trial in which 52% of the 87 patients given Ziihera saw improvements. The median duration of response was 14.9 months, determined by independent central review. Results were published in The Lancet in 2023.

Ziihera safety was demonstrated in the HERIZON-BTC-01 and ZWI-ZW25-101 trials, which enrolled 109 patients with biliary tract cancer and 124 patients with other cancers. The most common adverse reactions in HERIZON-BTC-01 were diarrhea (50%), abdominal pain (29%) and fatigue (24%).

"As a clinical investigator and medical oncologist focused on advancing the care of patients with biliary tract and liver cancers, I have experienced firsthand the significant unmet need for effective therapies for patients with these diseases," James Harding, M.D., associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center said in the news release. "[Ziihera] has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer.”

A phase 3 HERIZON-BTC-302 trial investigating the effectiveness of Ziihera in combination with standard-of-care therapy is ongoing. Ziihera effectiveness is also being testing on metastatic breast cancer tumors and gastroesophageal adenocarcinomas.

The wholesale acquisition cost WAC for Ziihere is $7,110 for a two-pack of two 300 mg bottles, according to the investor call. Financial assistance is available through JazzCares and commercially insured patients can pay as little as $10 per prescription using a savings card.