The field of Claudin 18.2-targeted therapies is rapidly advancing, offering new hope for patients with gastric and other cancers. Claudin 18.2 (CLDN18.2), an isoform of Claudin 18, is a tight junction protein family member. It is a highly selective biomarker that exhibits limited expression in normal tissues but is often abnormally expressed in various primary malignancies, including gastric cancer, gastroesophageal junction cancer, ovarian cancer, and some other solid tumors. This selective expression pattern makes it an attractive target for cancer therapy.
First Approved Therapy: Vyloy (Zolbetuximab)
The approval of Vyloy (zolbetuximab) in March 2024 marked a significant milestone as the first medication to target Claudin18.2. Developed by Ganymed Pharmaceuticals (later acquired by Astellas Pharma), Vyloy has been approved in the US, EU, and Japan for use in combination with chemotherapy as a first-line treatment for patients with HER2-negative G/GEJ adenocarcinoma whose tumors express Claudin18.2. Anticipated approval in China by the end of 2024 suggests a global expansion of this therapy.
Sales data for Vyloy indicated strong adoption, surpassing US$ 7 million by the end of Q3 2024. Zolbetuximab is now in clinical development, with trials investigating its application in combination with various therapy regimens and potential applications in tumors other than G/GEJ adenocarcinoma, such as pancreatic carcinoma.
Expanding Pipeline of Claudin 18.2-Targeting Therapies
Beyond Vyloy, numerous other Claudin18.2-targeting medicines are under development, including monoclonal antibodies, bispecific antibodies, CAR-T cell therapies, and antibody-drug conjugates (ADCs). Five of these candidates are already in phase 3 clinical trials, largely for G/GEJ malignancies, but research shows promise in other tumor types, including ovarian and lung cancers. The report indicates that over 60 drugs are currently in clinical trials targeting Claudin 18.2.
Competitive Landscape and Innovation
The competitive landscape for Claudin18.2-targeting therapies is becoming more dynamic, with major corporations investing in research and development. China has emerged as a hub of innovation, with companies like Innovent, MabWorks, and Biotheus making substantial progress in developing Claudin18.2-targeting medicines.
Companion Diagnostics
Companion diagnostic tests are an important element of the Claudin18.2-targeting therapeutic industry. Roche Diagnostics developed the Ventana CLDN18 (43-14A) RxDx Assay, the first immunohistochemistry-based test approved to detect Claudin18.2 expression in patients with G/GEJ adenocarcinoma. This test identifies which patients are most likely to benefit from Vyloy treatment, resulting in more precise and successful therapy selection. As the market for Claudin18.2-targeted therapies grows, the development and implementation of companion diagnostics will be critical in improving treatment results.
