U.S. FDA Grants Priority Review to BeOne Medicines’ TEVIMBRA in First-Line HER2+ GEA

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TEVIMBRA plus ZIIHERA and chemotherapy regimen delivered statistically significant median OS of 26.4 months, an unprecedented result in this challenging disease

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Results from the global Phase 3 HERIZON-GEA-01 study demonstrate potential to change clinical practice in advanced HER2+ gastroesophageal adenocarcinoma

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SAN CARLOS, Calif. — BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review to a supplemental Biologics License Application (sBLA) for TEVIMBRA^® (tislelizumab) in combination with ZIIHERA^® (zanidatamab) and chemotherapy for the first-line treatment of unresectable locally advanced/metastatic HER2-positive (HER2) gastric, gastroesophageal junction, or esophageal adenocarcinoma. The FDA has also granted Breakthrough Therapy Designation to the regimen of ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy, with and without TEVIMBRA, in this indication.

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Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors, BeOne Medicines, said:

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“HERIZON‑GEA‑01 has the potential to shift the treatment paradigm in this historically difficult-to-treat disease, with the TEVIMBRA-containing arm demonstrating an unprecedented 26-month survival benefit. The FDA’s Priority Review designation is a major milestone in our effort to bring better first‑line options to patients with HER2‑positive gastroesophageal adenocarcinoma. We will work in partnership with regulators to support the review process, with the aim of rapidly bringing this new treatment option to patients.”

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Data supporting sBLA filing

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The sBLA submission is based on the first interim analysis (IA1) of HERIZON-GEA-01, a global Phase 3 clinical trial designed to evaluate ZIIHERA plus chemotherapy, with and without TEVIMBRA, compared with the control arm of trastuzumab plus chemotherapy as first-line treatment for advanced/metastatic HER2+ GEA. Key findings of the trial include:

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Project Orbis pathway

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BeOne plans to participate in the FDA’s Project Orbis, an initiative that provides a framework for collaborative review of oncology products among international partners, for the submission of the HERIZON-GEA-01 data in territories in which BeOne holds the ZIIHERA license. With this pathway, BeOne aims to accelerate approval and patient access to this treatment, recognizing the global significance of the HERIZON‑GEA‑01 results, which demonstrated meaningful survival improvements in a disease where outcomes have remained largely unchanged for more than a decade.

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About the HERIZON-GEA-01 Phase 3 Trial

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HERIZON-GEA-01 ( NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with Jazz Pharmaceuticals, to evaluate and compare the efficacy and safety of ZIIHERA plus chemotherapy, with and without TEVIMBRA, to the standard of care (trastuzumab plus chemotherapy) as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: ZIIHERA in combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.

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About Gastroesophageal Adenocarcinoma

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Gastroesophageal adenocarcinoma (GEA), which includes cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide. Approximately 20% of GEA patients have HER2-positive disease^1,2,3, which has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 30% for gastric cancer and about 19% for GEA.⁴About ZIIHERA (zanidatamab) ZIIHERA (zanidatamab) is a bispecific human epidermal growth factor receptor 2, or HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.⁵ Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is approved in China for the treatment of patients who have unresectable, locally advanced, or metastatic HER2-high expression (IHC 3+) biliary tract cancer (BTC) and who have received prior systemic therapy. ZIIHERA has also been granted accelerated approval in the U.S. and conditional marketing authorization in the European Union for eligible BTC patients. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule. BeOne has licensed zanidatamab from Zymeworks in Asia (excluding India and Japan), Australia and New Zealand. Jazz Pharmaceuticals has rights in all other regions.