FDA Grants Accelerated Approval to Jazz Pharmaceuticals’ Ziihera for HER2-Positive Biliary Tract Cancer

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The FDA has granted accelerated approval to Jazz Pharmaceuticals’ Ziihera (zanidatamab-hrii) for previously treated, human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer (BTC). The regulatory action for the bispecific antibody provides a chemotherapy-free option for this patient population with improved quality of life.¹

"BTC is a devastating disease with a poor prognosis and five-year survival rates under 5% in the metastatic setting. Patients with unresectable or metastatic HER2-positive BTC have had a high unmet need with limited treatment options and few approved therapies," Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, said in a press release. "The approval of Ziihera, which previously received Breakthrough Therapy Designation from the FDA for this indication, 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, with the goal of improving outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers."¹

Earlier this year in April, Jazz submitted a Biologics License Application (BLA) to the FDA seeking the accelerated approval of Ziihera, which the agency then granted with Priority Review status.^2,3 The BLA was based on data from the Phase IIb HERIZON-BTC-01 trial (NCT04466891), which the agency also based the approval on.

The trial analyzed Ziihera as a monotherapy in patients previously treated for HER2-positive BTC, representing the largest Phase IIb clinical trial to date conducted specifically in this patient population. Investigators enrolled patients aged at least 18 years who received prior treatment with a gemcitabine-containing regimen but who were not previously treated with HER2-targeted therapies.

Data presented at the 2024 ASCO Annual Meeting show that among the overall evaluable patient population enrolled in cohort 1 (n = 80), the confirmed objective response rate (cORR) was 41.3%, with a disease control rate of 68.8%.⁴ The cORR was 51.6% in a subgroup of patients with HER2-positive IHC 3+ disease and 5.6% in patients with IHC 2+ disease. Across a median follow-up of 22 months (range, 16-34), median duration of response increased to 14.9 months (95% CI, 7.4-not reached).

Median overall survival (OS) in the overall population in cohort 1 was 15.5 months (95% CI, 10.4-18.5). OS was 18.1 months (95% CI, 12.2-23.2) in patients with HER2-positive IHC 3+ disease, and 5.2 months (95% CI, 3.1-10.2) in patients with IHC 2+ disease. The 12-month OS rates were 56.2% in the overall population (95% CI, 44.3%-66.5%), 65.0% in the IHC 3+ subgroup (95% CI, 51.6%-75.6%), and 20.8% in the IHC 2+ subgroup (95% CI, 5.1%-43.7%).

"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, MD, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center, said in a press release. "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."¹

References

1. Jazz Pharmaceuticals announces U.S. FDA approval of Ziihera® (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC). News release. Jazz Pharmaceuticals. November 20, 2024. Accessed November 21, 2024. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-ziiherar

2. Pant S, Fan J, Oh D-Y, et al. Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. J Clin Oncol. 2024;42(suppl 16):4091. doi:10.1200/JCO.2024.42.16_suppl.4091

3. Jazz Pharmaceuticals Completes Zanidatamab Biologics License Application for Previously Treated HER2-Positive Metastatic Biliary Tract Cancer. Jazz Pharmaceuticals. April 2, 2024. Accessed November 21, 2024. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-completes-zanidatamab-biologics-license

4. Jazz Pharmaceuticals Completes Biologics License Application for Zanidatamab for HER2-Positive Metastatic Biliary Tract Cancer. PharmExec. April 2, 2024. Accessed November 21, 2024. https://www.pharmexec.com/view/jazz-pharmaceuticals-completes-biologics-license-application-for-zanidatamab-for-her2-positive-metastatic-biliary-tract-cancer