FDA Approves Jazz's Ziihera in First-Line HER2+ GEA, Setting a New Standard of Care

The FDA on Tuesday approved Jazz Pharmaceuticals’ Ziihera (zanidatamab-hrii) for first-line treatment of HER2-positive gastroesophageal adenocarcinoma (GEA), clearing two regimens that together establish a new front-line standard of care in a cancer diagnosed in roughly 31,000 U.S. patients each year.

The approval covers Ziihera plus BeOne Medicines’ Tevimbra (tislelizumab) and fluoropyrimidine- and platinum-containing chemotherapy for tumors that are HER2+ IHC 3+ or IHC 2+/ISH+, and Ziihera plus chemotherapy for HER2+ IHC 3+ disease. Both are approved regardless of PD-L1 status, making Ziihera the first and only bispecific HER2-targeted antibody cleared in the front-line GEA setting.

The decision lands on the drug’s August 25 PDUFA date and follows the Phase 3 HERIZON-GEA-01 trial, published in the New England Journal of Medicine and first presented at ASCO GI 2026. The Ziihera combinations cut the risk of disease progression or death by 35%, extending median progression-free survival to 12.4 months versus 8.1 months for trastuzumab plus chemotherapy. The triplet arm showed a 28% reduction in the risk of death, with median overall survival of 26.4 months versus 19.2 months, a greater-than-seven-month gain and the longest median survival reported in a Phase 3 trial in HER2+ advanced GEA.

Trastuzumab plus chemotherapy has been the standard of care since 2010. Ziihera’s bispecific design binds two distinct HER2 epitopes, and the data translate into a 7.2-month overall survival improvement over the incumbent.

Jazz shares rose about 3.5% in Tuesday trading to roughly $263. The approval expands Ziihera’s footprint from its existing indication, previously treated HER2-positive biliary tract cancer, which generated $24.8 million in full-year 2025 sales. The new label reaches a much larger population, as roughly 20% of GEA patients have HER2-positive disease.

Safety mirrors prior zanidatamab studies. Diarrhea was the most common adverse reaction, managed with loperamide prophylaxis and dose modifications, with few Ziihera discontinuations. The label carries boxed warnings for diarrhea and embryo-fetal toxicity.

For context on the data and why the label matters to the broader Jazz story, see our pre-decision analysis of the Ziihera GEA PDUFA. Jazz will host an investor webcast Tuesday at 4:30 p.m. ET to discuss the approval and the zanidatamab development program.