Metastatic HER2-negative gastric and gastroesophageal junction (GEJ) adenocarcinoma is notoriously difficult to treat and has a significant unmet need for new efficacious treatments. In contrast to HER2-positive disease (for which HER2-targeted agents such as trastuzumab [Genentech] and ENHERTU® [Daiichi Sankyo] are available), targeted treatment options are more limited for HER2-negative patients. Zolbetuximab would address some of that unmet need as a first-in-class claudin 18.2 (CLDN18.2) inhibitor in oncology as well as first-line metastatic HER2-negative gastric or GEJ adenocarcinoma. CLDN18.2 was found to be highly expressed in ~38% of HER2-negative gastric cancer patients in two phase 3 trials (SPOTLIGHT and GLOW). Zolbetuximab also has the potential to treat pancreatic cancer, in which 50% of cases have CLDN18.2 expression.
Claudin 18.2 (CLDN18.2) has emerged as an exciting target to treat gastric cancers because alterations in claudin expression can affect signaling pathways and help promote tumors. Zolbetuximab is poised to be the first-in-class CLDN18.2 inhibitor to enter the oncology market and to offer a much-needed biomarker-driven option for first-line treatment of metastatic HER2-negative gastric or GEJ adenocarcinoma. Regulatory submissions were based on the positive results from two phase 3 trials conducted in previously untreated CLDN18.2-positive, HER2-negative, unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma:
The incidence of serious treatment-emergent adverse events (TEAEs) in both studies was similar between the groups and consistent with previous studies.
November 2010
November 2012
September 2022
June 2023
July 2023
January 12, 2024
Expected launch:
Patents estimated to expire beginning in 2032
How will zolbetuximab impact the market for gastric and GEJ adenocarcinomas?
What gaps in treatment does zolbetuximab fill?
Early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions. As result, gastric cancer is often diagnosed in the advanced or metastatic stage when it has spread to other body tissues or organs. The five-year relative survival rate for patients at the metastatic stage is 6.6%. Despite approvals of targeted therapies and immunotherapies, improving survival in gastric cancer remains a critical unmet need as few patients survive more than 2 years after initiation of front-line therapy. In addition, metastatic HER2-negative gastric or GEJ adenocarcinoma is notoriously difficult to treat. CLDN18.2 has emerged as a promising target for treating gastric cancers, and zolbetuximab could be an important new option in the largely untapped HER2-negative gastric and GEJ adenocarcinoma market segment.
What hurdles might it need to overcome to reach blockbuster status?
– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of December 15, 2023
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