FDA Approves Zymeworks' Bispecific Antibody Ziihera for First-Line HER2+ Gastroesophageal Cancer

The FDA has approved two zanidatamab-hrii (Ziihera)-containing regimens for adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA): Ziihera plus Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for HER2+ IHC 3+ and IHC 2+/ISH+ disease, and Ziihera plus chemotherapy alone for HER2+ IHC 3+ disease.¹ Zymeworks discovered and engineered zanidatamab, with global development and commercialization now handled by partners Jazz Pharmaceuticals and BeOne Medicines under separate licensing agreements.¹

How does Ziihera work, and what does the trial data show?

Ziihera is a bispecific HER2-directed antibody that binds two distinct extracellular sites on HER2 simultaneously, enabled by Zymeworks' proprietary Azymetric platform.¹ This binding drives internalization and reduced HER2 expression on the tumor cell surface, while also inducing complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, mechanisms that together produce tumor growth inhibition and cell death.¹

The approval is supported by the Phase 3 HERIZON-GEA-01 trial, published in the New England Journal of Medicine and first presented at ASCO GI 2026; BioPharm International© covered that publication in detail when it was released.² "The median overall survival of more than two years observed with this regimen is encouraging and represents meaningful progress for patients and their families," said Jaffer A. Ajani, MD, professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center. "Importantly, similar outcomes were observed regardless of PD-L1 status, suggesting that this regimen may provide a treatment option for a broad range of patients with HER2-positive disease."¹

How was zanidatamab discovered?

Ziihera was discovered and engineered by Zymeworks' research team in Vancouver using the company's Azymetric platform, and advanced through preclinical and clinical development under its own investigational new drug application before Zymeworks entered licensing agreements with BeOne Medicines in 2018 and Jazz Pharmaceuticals in 2022.¹ This is the second FDA approval for Ziihera in under two years, following its earlier accelerated approval in biliary tract cancer.¹ Bispecific antibodies still represent a small fraction of approved biologics relative to what's moving through earlier development. "Within the FDA-approved products, there's a minimal amount right now that... are bispecifics. However, when you look at the pipeline of products that are coming through in Phase I, Phase II, there's an enormous wave of these complex proteins that are coming through," said Atul Mohindra, head of biologics R&D at Lonza, in earlier BioPharm International coverage of the bispecific antibody field broadly, unrelated to zanidatamab specifically.³

"This second FDA approval for zanidatamab represents a significant milestone for Zymeworks and reinforces the strength of our scientific innovation engine," said Kenneth Galbraith, chair and chief executive officer of Zymeworks. "Zanidatamab was discovered in our Vancouver laboratories using our proprietary Azymetric platform and advanced by our development team into late-stage development, and today's approval demonstrates how our science can translate into meaningful new treatment options for patients around the world."¹

What does this mean financially for Zymeworks?

The approval triggers a $250 million milestone payment from Jazz Pharmaceuticals, bringing cumulative payments from Jazz to $650 million, with Zymeworks eligible for up to $1.3 billion in additional milestones and tiered royalties of 10% to 20% on net sales in Jazz's territories.¹ Under its separate BeOne Medicines collaboration, Zymeworks has received $81 million to date and remains eligible for up to $144 million in additional milestones plus royalties of up to 19.5% in BeOne's licensed territories.¹

Why does this approval matter for GEA patients?

GEA, encompassing cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide, with roughly 20% of patients having HER2+ disease; more than 31,000 new stomach cancer cases are diagnosed annually in the US.¹ Prognosis for metastatic GEA remains poor, with a global five-year survival rate below 10%.¹

What's next?

Additional clinical trials of Ziihera across other tumor types remain underway through Jazz Pharmaceuticals and BeOne Medicines, and the HERIZON-GEA-01 trial continues with further analyses planned.¹ Zymeworks is also advancing a wholly owned pipeline of trispecific T-cell engagers and antibody-drug conjugates.¹

References

1. U.S. FDA approves Ziihera (zanidatamab-hrii) with and without tislelizumab plus chemotherapy in first-line HER2+ advanced gastroesophageal adenocarcinoma. News release. Zymeworks Inc.; August 25, 2026. Accessed August 25, 2026.
2. Phase 3 HERIZON-GEA-01 data published in NEJM reinforce zanidatamab's potential in HER2-positive gastroesophageal cancer. BioPharm International. Accessed August 25, 2026.
3. The challenges, successes, and future of bispecific antibodies. BioPharm International. Published December 31, 2024. Accessed August 25, 2026.