Ziihera Phase 3 Results Spur sBLA Push
Ziihera Phase 3 results showed survival gains in HER2-positive GEA and led Jazz to plan a U.S. sBLA, accelerating review and reshaping first-line prospects.
KEY TAKEAWAYS
- Ziihera Phase 3 showed significant PFS gains and a triplet OS benefit versus trastuzumab.
- Jazz plans a U.S. supplemental BLA targeting first-line approval in first half of 2026.
- No new safety signals were observed and benefits were seen regardless of PD-L1 status.
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Ziihera Phase 3 results published Nov. 17, 2025, show Zymeworks Inc.’s (ZYME) bispecific HER2 antibody produced statistically significant progression-free survival gains and a significant overall survival benefit in the triplet arm. Jazz Pharmaceuticals said it will pursue a U.S. supplemental Biologics License Application (sBLA) in the first half of 2026.
Phase 3 Efficacy, Safety, and Response
The HERIZON-GEA-01 Phase 3 trial evaluated zanidatamab-hrii (Ziihera) plus chemotherapy, with or without the PD-1 inhibitor Tevimbra (tislelizumab), as first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including tumors of the stomach, gastroesophageal junction, and esophagus. Both Ziihera regimens produced statistically significant and clinically meaningful improvements in progression-free survival compared with trastuzumab plus chemotherapy. The triplet regimen with Tevimbra also achieved a statistically significant overall survival advantage, while the doublet showed a strong trend toward significance at the interim analysis.
Objective response rate and duration of response improved in both Ziihera arms, with benefit observed regardless of PD-L1 status. The safety profile remained consistent with known risks for the agents used, and no new safety signals emerged in either experimental arm.
Regulatory Path and Partnerships
Jazz Pharmaceuticals plans to submit a supplemental Biologics License Application in the U.S. to seek first-line approval for Ziihera, according to the partner statement. Full data from the trial will be presented at a major medical meeting in 2026, and an interim overall survival analysis for the doublet arm is expected midyear.
Ziihera is licensed to Jazz Pharmaceuticals outside Asia, Australia, and New Zealand, and to BeOne Medicines in Asia, Australia, and New Zealand. Both partners will engage health authorities in their territories regarding potential label expansion. Zymeworks receives milestone payments and tiered royalties from these agreements and maintains a strong cash position with a projected runway into the second half of 2027.
Ziihera is already approved in the U.S., European Union, and China for second-line biliary tract cancer. No regulatory approvals for first-line GEA have been granted as of the latest disclosures.
“Both Ziihera plus chemotherapy and Ziihera plus tislelizumab and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival compared to the control arm, trastuzumab plus chemotherapy,” the company said in its Nov. 17 press release.
