Key Takeaways:
The U.S. FDA approved Jazz Pharmaceuticals' Ziihera (zanidatamab-hrii) with tislelizumab and chemotherapy for first-line HER2+ gastroesophageal adenocarcinoma, cutting death risk 28%.
"This approval is a major step forward for people with HER2+ advanced GEA," Rob Iannone, executive vice president and chief medical officer at Jazz Pharmaceuticals, said. "Ziihera is now the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2+ advanced GEA patients, regardless of PD-L1 status."
The decision rests on the Phase 3 HERIZON-GEA-01 trial, published in the New England Journal of Medicine. Median overall survival reached 26.4 months versus 19.2 months with trastuzumab plus chemotherapy, a 28 percent lower risk of death (hazard ratio 0.72). Median progression-free survival reached 12.4 months versus 8.1 months, a 35 percent lower risk of progression or death (hazard ratio 0.63). The FDA cleared two regimens: Ziihera plus Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ and IHC 2+/ISH+ patients, and Ziihera plus chemotherapy for HER2+ IHC 3+ patients.
GEA, which includes gastric, gastroesophageal junction and esophageal cancers, is the fifth most common cancer worldwide, with roughly 20 percent of patients HER2-positive. More than 31,000 new stomach cancer cases are diagnosed in the U.S. each year, and the five-year survival rate for metastatic disease is below 10 percent. The approval expands Jazz's oncology portfolio beyond biliary tract cancer, where Ziihera was already cleared.
Similar outcomes appeared in PD-L1 positive and negative subgroups, suggesting the regimen can benefit a broad range of patients, said Geoffrey Ku, study co-author and associate attending physician at Memorial Sloan Kettering Cancer Center. He called HER2 testing at diagnosis critical to guiding treatment selection.
The U.S. prescribing information carries boxed warnings for diarrhea and embryo-fetal toxicity. Diarrhea was reported in 85 percent of 330 patients receiving Ziihera with chemotherapy and tislelizumab, including grade 4 events in 2.1 percent and fatal outcomes in 1.5 percent. Loperamide prophylaxis was administered during the first cycle.
Zanidatamab is being developed by Jazz and BeOne Medicines under license agreements from Zymeworks. The FDA has granted three Breakthrough Therapy designations and two Fast Track designations for the drug, which is also approved in the European Union.
The approval gives Jazz a new front-line franchise in a cancer with few options, setting Ziihera against trastuzumab-based regimens that have dominated HER2+ GEA for more than a decade. Investors will watch the company's webcast on Aug. 25 at 4:30 p.m. ET for updates on the zanidatamab program and potential peak-sales guidance.
This article is for informational purposes only and does not constitute investment advice.
