Wednesday, March 27, 2024
Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura) announced on March 26, 2024, that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved VYLOY™ (zolbetuximab), an anti-claudin 18.2 (CLDN18.2) monoclonal antibody, for patients with CLDN18.2 positive, unresectable, advanced, or recurrent gastric cancer. VYLOY becomes the first and only CLDN18.2-targeted therapy sanctioned by any regulatory agency globally.
Gastric cancer poses a significant health challenge in Japan, often diagnosed in its advanced stages due to symptoms resembling common stomach ailments. Despite efforts to curb its impact, gastric cancer ranks as the third most lethal cancer in Japan, with 126,724 cases identified in 2022.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, expressed enthusiasm for the approval, hailing it as a breakthrough in gastric cancer treatment. She emphasized Astellas' commitment to addressing the urgent need for effective therapies in Japan, where gastric cancer incidence rates are alarmingly high. Chatterjee-Kishore highlighted the potential of VYLOY to extend valuable time with loved ones, aligning with Astellas' mission to enhance patient outcomes.
Kohei Shitara, MD, Primary Investigator for the SPOTLIGHT Trial and Head of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, emphasized the significance of developing targeted therapies for advanced gastric adenocarcinoma. As the lead investigator for the Phase 3 SPOTLIGHT clinical trial, Shitara witnessed firsthand the remarkable improvements in progression-free survival and overall survival among patients treated with VYLOY in combination with chemotherapy. He stressed the importance of this new treatment option for CLDN18.2-positive patients in Japan, where gastric cancer claimed nearly 44,000 lives in 2022.
The approval stems from the positive outcomes of the Phase 3 SPOTLIGHT and GLOW clinical trials, focusing on first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors tested positive for CLDN18.2. Both trials demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) among patients receiving VYLOY in combination with chemotherapy compared to those receiving chemotherapy alone. The most common treatment-emergent adverse events included nausea, vomiting, decreased appetite, neutropenia, and decreased weight, managed through appropriate measures.
Approximately 38% of screened patients in both trials had CLDN18.2-positive tumors. CLDN18.2 positivity was defined as ≥75% of tumor cells exhibiting moderate-to-strong membranous CLDN18 staining, confirmed by experienced pathologists or laboratories using approved diagnostic assays. Astellas collaborated with Roche Diagnostics to develop the VENTANA® CLDN18 (43-14A) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic test to identify eligible patients for VYLOY treatment. The test will be available initially in Japan and is expected to expand to additional laboratories.
Astellas has submitted applications for VYLOY to regulatory agencies worldwide, with ongoing reviews. The impact of this approval has already been factored into Astellas' financial forecast for the current fiscal year ending March 31, 2024.
VYLOY (zolbetuximab) is an anti-claudin 18.2 (CLDN18.2) monoclonal antibody approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) for patients with CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer. It is used in combination with chemotherapy for patients with HER2-negative tumors. VYLOY is the first and only CLDN18.2-targeted therapy approved globally. CLDN18.2 positivity should be confirmed using approved diagnostic assays. VYLOY binds to CLDN18.2 expressed on cancer cell membranes, exhibiting antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to tumor growth inhibition.
SPOTLIGHT and GLOW were Phase 3 clinical trials evaluating the efficacy and safety of VYLOY in combination with chemotherapy for first-line treatment of CLDN18.2-positive gastric or GEJ adenocarcinoma. Both trials demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone.
Astellas is also conducting investigational studies targeting CLDN18.2 in metastatic pancreatic adenocarcinoma, with ongoing trials evaluating the safety and efficacy of zolbetuximab in combination with other treatments.
Overall, the approval of VYLOY represents a significant advancement in the treatment landscape for gastric cancer, offering hope to patients in Japan and potentially worldwide.
Source: astellas.com
