Jazz Pharmaceuticals reported that its bispecific antibody Ziihera (zanidatamab‑hrii) achieved a median overall survival of 26.4 months in the HERIZON‑GEA‑01 Phase 3 trial, a 7‑month improvement over the 19.2 months observed with trastuzumab plus chemotherapy. The hazard ratio for death was 0.72 (p = 0.0043), indicating a 28 % reduction in the risk of death for patients receiving the Ziihera‑based regimen. Progression‑free survival was 12.4 months for both Ziihera arms, compared with 8.1 months for the trastuzumab control, with hazard ratios of 0.65 and 0.63 for the doublet and triplet arms respectively. Objective response rates were 70.7 % for the triplet, 69.6 % for the doublet, and 65.7 % for trastuzumab. Grade ≥ 3 treatment‑related adverse events occurred in 71.8 % of patients in the triplet arm, 59.0 % in the doublet arm, and 59.6 % in the control arm; discontinuations due to adverse events were 11.9 %, 8.5 %, and 2.3 % respectively.
The study enrolled 914 patients across more than 30 countries and compared three treatment arms: Ziihera plus chemotherapy, Ziihera plus chemotherapy and the PD‑1 inhibitor tislelizumab, and trastuzumab plus chemotherapy. The trial’s primary endpoints were overall survival and progression‑free survival, both of which favored the Ziihera‑based regimens. Notably, the doublet arm’s overall survival did not reach statistical significance at the interim analysis, a nuance that tempered enthusiasm for the incremental benefit of adding tislelizumab.
Ziihera’s dual HER2‑targeting mechanism—binding two extracellular sites on the HER2 receptor—promotes receptor internalization and triggers complement‑dependent cytotoxicity, antibody‑dependent cellular cytotoxicity, and phagocytosis. The drug received accelerated FDA approval in November 2024 for previously treated, unresectable or metastatic HER2‑positive biliary tract cancer, establishing a regulatory precedent that could facilitate future approvals in gastroesophageal adenocarcinoma.
The trial results position Ziihera as a potential new standard of care for first‑line HER2‑positive GEA, a disease with limited therapeutic options. While the overall survival benefit of the triplet arm is statistically significant, the modest incremental advantage over the doublet arm and the lack of significance for the doublet’s OS at interim have led some investors to question the added value of tislelizumab. Nonetheless, the substantial improvements in progression‑free survival and objective response rates, coupled with a safety profile consistent with known data, strengthen the case for regulatory submissions and commercial launch.
Management emphasized the clinical significance of the findings, stating that “Ziihera plus tislelizumab and chemotherapy should become the new standard of care for patients with HER2‑positive first‑line locally advanced unresectable or metastatic GEA.” The company highlighted the trial’s global reach and the robustness of the data set as evidence of Ziihera’s potential to reshape treatment patterns.
The results will be presented at the 2026 ASCO Gastrointestinal Cancers Symposium on January 8, 2026. Following the presentation, Jazz Pharmaceuticals is expected to file a New Drug Application with the FDA and the European Medicines Agency, potentially opening a new revenue stream and expanding its oncology portfolio. The company’s prior approval for biliary tract cancer and the positive Phase 3 data in GEA suggest a trajectory toward broader market penetration and increased shareholder value.
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