Astellas’ VYLOY™ Receives FDA Approval, Paving The Way For Advanced Gastric Cancer Treatment

Astellas Pharma Inc. (TSE: 4503) has announced that its innovative therapy, VYLOY™ (zolbetuximab-clzb), has received approval from the U.S. Food and Drug Administration (FDA). VYLOY™ is approved for use in combination with fluoropyrimidine and platinum-based chemotherapy as a first-line treatment for adults with locally advanced, unresectable, or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. The treatment specifically targets patients whose tumors are positive for claudin (CLDN) 18.2, as identified through an FDA-approved diagnostic test. This marks a significant milestone, as VYLOY™ becomes the first and only CLDN18.2-targeted therapy approved in the United States.

In the SPOTLIGHT and GLOW Phase 3 clinical trials, about 38% of screened patients had CLDN18.2-positive tumors. CLDN18.2 positivity is identified when ≥75% of tumor cells show moderate to membranous solid staining using the VENTANA® CLDN18 (43-14A) RxDx Assay from Roche. Astellas collaborated on the newly approved immunohistochemistry (IHC) companion diagnostic (CDx) test, for identification of patients eligible for VYLOY. 

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas, said in a statement, “The approval of VYLOY as the first and only targeted therapy for CLDN18.2-positive patients in the U.S. further delivers on our relentless pursuit of scientific progress for devastating diseases like gastric and GEJ cancers, which are often only discovered at the advanced stage. This achievement is the result of years of dedicated research and development focused on targeting a novel biomarker, and we are grateful to the patients, investigators, and Astellas team members who have made this important advancement for patients a reality.”

Samuel J. Klempner, M.D., Associate Professor, Harvard Medical School, Medical Oncologist at Massachusetts General Hospital, Boston, commented, “While there have been advances in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ cancers in the last several years, there is still a tremendous unmet need among our patients. The approval of VYLOY, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive and for those on the frontlines of treatment decision-making.”

The GLOW analyzed VYLOY’s combination with CAPOX, a chemotherapy regimen that included capecitabine and oxaliplatin, compared to placebo plus CAPOX. The SPOTLIGHT study estimated VYLOY and mFOLFOX6, a combination chemotherapy that includes oxaliplatin, leucovorin, and fluorouracil, compared to placebo plus mFOLFOX6. The trials demonstrated that VYLOY when combined with chemotherapy, improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone. The most common treatment-emergent adverse events (TEAEs) across the trials reported were nausea, vomiting, and decreased appetite.

The VENTANA CLDN18 (43-14A) RxDx Assay is an FDA-approved immunohistochemistry test to identify patients eligible for VYLOY treatment. Testing is available across several U.S. reference labs, with plans to expand further. Following the FDA's approval, VYLOY is now authorized in five regions globally: Japan, the UK, the EU, South Korea, and the U.S. The first global approval was granted in Japan in March 2024, followed by UK, EU, and South Korea approvals. Astellas has submitted additional applications for VYLOY to regulatory agencies worldwide.  The company has already accounted for this approval in its financial forecast for the fiscal year ending March 31, 2025.