FDA Approves Jazz Pharmaceuticals' Ziihera (Zanidatamab) for First-Line HER2+ Gastroesophageal Cancer — Longest Median Overall Survival Ever Reported in a Phase 3 Trial for the Setting

The FDA approved Ziihera (zanidatamab-hrii), Jazz Pharmaceuticals' bispecific HER2-directed antibody, in two first-line regimens for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA): Ziihera plus tislelizumab (Tevimbra) plus fluoropyrimidine/platinum chemotherapy for HER2 IHC 3+ and IHC 2+/ISH+ tumors regardless of PD-L1 status, and Ziihera plus chemotherapy alone (without tislelizumab) for HER2 IHC 3+ tumors. The approval, which hit its August 25, 2026 PDUFA target action date, was based on the Phase 3 HERIZON-GEA-01 trial (914 patients), which showed progression-free survival of 12.4 months versus 8.1 months for the comparator (35% risk reduction) and overall survival of 26.4 months versus 19.2 months (28% risk reduction) — the longest median overall survival ever reported in a Phase 3 trial in this setting. The most common adverse reaction was diarrhea, managed with loperamide prophylaxis and antidiarrheals, with few discontinuations. Ziihera already held accelerated approval in previously treated biliary tract cancer; this expands it into a first-line, all-comers HER2+ GEA population.