Astellas Gets EU Nod for VYLOY™ with Chemo in Advanced Gastric and Gastroesophageal Cancer

Astellas Pharma Inc. has announced that the European Commission has approved VYLOY™ (zolbetuximab) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are positive for claudin (CLDN) 18.2. The European Medicines Agency supports maintaining zolbetuximab's designation as an orphan medicinal product due to the poor survival outcomes associated with these cancers.

Zolbetuximab is the first and only approved monoclonal antibody designed to target gastric tumor cells expressing the CLDN18.2 biomarker, marking a significant advancement in personalized cancer treatment. Clinical trials revealed that approximately 38% of adult patients with advanced gastric and GEJ cancers have tumors that are CLDN18.2 positive. By binding to CLDN18.2 on tumor cell membranes, zolbetuximab induces antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and inhibits tumor growth.

Zorana Maravic, CEO of Digestive Cancers Europe, highlighted the challenges in diagnosing gastric and GEJ cancers at non-advanced stages due to their symptoms resembling more common stomach conditions. Timely diagnosis and personalized treatment are essential for improving patient survival and quality of life.

Moitreyee Chatterjee-Kishore, Senior Vice President and Head of Immuno-Oncology Development at Astellas, expressed excitement about introducing zolbetuximab in Europe. She emphasized that this marks a new era in precision medicine for advanced gastric and GEJ cancers, reflecting Astellas' commitment to scientific innovation and enhanced patient outcomes.

Data from the Phase 3 SPOTLIGHT and GLOW clinical trials supported the European Marketing Authorization for zolbetuximab. These trials demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) for patients treated with zolbetuximab compared to standard chemotherapies. In the SPOTLIGHT trial, zolbetuximab combined with mFOLFOX6 achieved a median PFS of 10.61 months versus 8.67 months with placebo plus mFOLFOX6, with median OS at 18.23 months against 15.54 months, respectively. Similarly, the GLOW trial reported a median PFS of 8.21 months versus 6.80 months and a median OS of 14.39 months versus 12.16 months, with zolbetuximab plus CAPOX compared to placebo plus CAPOX.

The European Marketing Authorization for zolbetuximab is effective in all 27 EU member states and additional countries such as Iceland, Liechtenstein, and Norway. It aligns with the recent updates to the ESMO Gastric Cancer Living Guidelines, which now recommend considering zolbetuximab combined with chemotherapy for patients with CLDN18.2 positive, HER2-negative tumors in the first-line metastatic disease treatment. Astellas is collaborating with local regulatory authorities and health technology assessment bodies across the EU to facilitate patient access to this novel treatment.

This approval in Europe follows the UK's Medicines and Healthcare products Regulatory Agency's approval in August 2024 and Japan's Ministry of Health, Labour and Welfare's approval in March 2024. Astellas has also submitted applications for zolbetuximab to other global regulatory agencies, with reviews ongoing.

About Zolbetuximab:
Zolbetuximab is a claudin 18.2-directed cytolytic antibody, evaluated in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment in adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma with CLDN18.2-positive tumors. In the SPOTLIGHT and GLOW Phase 3 trials, 38% of patients had CLDN18.2 positive tumors. Astellas collaborated with Roche on the VENTANA® CLDN18 (43-14A) RxDx Assay, which is intended to identify patients eligible for zolbetuximab treatment, pending approval.

About Gastric and GEJ Cancer:
Gastric and GEJ cancers are histologically similar and are managed similarly in treatment guidelines, often showing similar treatment responses. In 2022, over 135,000 new cases of gastric and GEJ cancer were diagnosed in Europe, making it the sixth most common cause of cancer-related mortality. Early diagnosis is critical as these cancers are often detected at advanced or metastatic stages due to overlapping symptoms with more common stomach conditions. Risk factors for these cancers include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease.