FDA Approves Ziihera as First Dual HER2-Targeted Therapy for Biliary Tract Cancer

The US Food and Drug Administration (FDA) has granted accelerated approval to Ziihera (zanidatamab-hrii), a novel therapy for adults with previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC).  The approval was based on a 52% objective response rate and a median duration of response of 14.9 months, as observed in the pivotal HERIZON-BTC-01 clinical trial.

Developed by Jazz Pharmaceuticals, Ziihera's approval marks a significant milestone as it is the first and only dual HER2-targeted bispecific antibody approved in the U.S. for this purpose. The trial findings, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet Oncology, highlight Ziihera's potential. Ziihera is a promising option for this hard-to-treat cancer population, which currently faces five-year survival rates below 5% in metastatic settings.

A Breakthrough in Biliary Tract Cancer Treatment

Biliary tract cancer, a group of rare and aggressive cancers, has historically had limited treatment options and a poor prognosis. The approval of Ziihera offers a chemotherapy-free alternative, targeting two distinct HER2 epitopes, which are overexpressed in a subset of BTC cases. This innovative approach has demonstrated significant efficacy in the largest Phase 2b clinical trial for this patient group to date.

Dr. Rob Iannone, Executive VP and Chief Medical Officer at Jazz Pharmaceuticals, highlighted the impact of this approval, stating, “BTC is a devastating disease with a poor prognosis and five-year survival rates under five percent in the metastatic setting... The approval of Ziihera is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC. We look forward to advancing research of zanidatamab in BTC and other HER2-expressing solid tumors,”

Clinical Trial Insights

The HERIZON-BTC-01 trial assessed the efficacy of Ziihera in 62 patients with HER2-positive BTC, achieving a confirmed objective response rate of 52%. The trial not only met its primary endpoints but also provided hope for improved survival outcomes, with a median duration of response nearing 15 months.

The trial was conducted across 32 clinical sites in nine countries, providing a broad base of data and reflecting a diverse patient demographic. The promising results have paved the way for the ongoing Phase 3 confirmatory trial, HERIZON-BTC-302, which will further evaluate Ziihera in combination with standard-of-care therapies.

Patient and Community Impact

Dr. James Harding, a medical oncologist at Memorial SKCC, expressed optimism about the new treatment option, noting, “Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer.”

"Metastatic biliary tract cancer, BTC, places a significant burden on patients, affecting their quality of life and their emotional and mental well-being, as well as that of their families," said Stacie Lindsey, CEO and founder of the Cholangiocarcinoma Foundation. “The approval of Ziihera offers a promising treatment option. It provides patients and their loved ones the possibility of more time together and an improved quality of life, which is invaluable for the entire BTC community.”

Safety Profile and Future Research

Ziihera's safety profile was evaluated in 80 patients, with common side effects including diarrhea, abdominal pain, and fatigue. Serious adverse reactions were observed in 53% of participants, including biliary obstruction, infections, and, in one case, fatal hepatic failure. The FDA has issued a boxed warning regarding embryo-fetal toxicity, advising patients to use effective contraception.

Looking ahead, Jazz Pharmaceuticals is conducting the Phase 3 HERIZON-BTC-302 trial to confirm Ziihera’s clinical benefits in combination with standard-of-care therapies. Additionally, zanidatamab is being explored for other HER2-expressing cancers, including metastatic breast and gastroesophageal cancers.

About Author: Tracy Mokwe

With over 3 years of experience as a medical laboratory scientist and writer, I am passionate about translating complex scientific information into clear and accessible content. My expertise lies in medical sciences, laboratory science and research, digital health, AI, and cybersecurity in healthcare.