Eisai's Potential First-in-Class Oral Cancer Drug E7386 Granted Clinical Trial Approval in China for Endometrial Cancer

Dec 04, 2024 16:36 CST Updated 16:36

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Today (December 4), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,Eisai's Class 1 new drug E7386 has received implied permission for clinical trials.Indications areCombination of Lenvatinib Mesylate Capsules for the Treatment of Endometrial Cancer. According to publicly available information from Eisai,E7386Is aPotential "first-in-class"Novel Oral Anticancer Drugs,A CBP/β-catenin protein-protein interaction inhibitor, co-developed by Eisai and PRISM BioLab.According to the query on the CDE official website, this is the first time that the drug has been approved for clinical use in China.

Screenshot source: CDE official website

β-catenin is considered one of the "undruggable" targets that are difficult to develop into new drugs.E7386 inhibits the binding of β-catenin to its transcriptional coactivator CBP (CREB-binding protein), thereby modulating Wnt/β-catenin signaling.。Since this product is considered to act on the CBP/β-catenin transcription complex located at the very downstream of the Wnt signaling pathway, it is expected to not only inhibit ligand-dependent activation but also suppress activation caused by Wnt signaling factors such asAPCAndβ-cateninActivation caused by gene mutation.

According to the public information provided by Eisai Co., Ltd.,In preclinical studies, E7386 demonstrated favorable activity (such as modulating tumor angiogenesis, altering the immune microenvironment, and inhibiting tumor growth).E7386 is also expected to release the suppression on tumor-infiltrating T cells by activating the Wnt signaling pathway and enhance the effect of immune checkpoint inhibitors.

Lenvatinib is an orally available multiple kinase inhibitor. Exploratory tumor biomarker analyses have previously suggested that the combination of E7386 and lenvatinib may influence the tumor microenvironment in patients by affecting Wnt signaling, angiogenesis, hypoxia response, and glycolysis pathways.

At the 2024 European Society for Medical Oncology (ESMO) Congress, researchers announced the latest clinical study results of the combination therapy of E7386 and Lenvatinib. To determine the efficacy of E7386 in combination withLenvatinibIn the open-label Phase 1b study, the recommended dose by Eisai isPatients with advanced endometrial cancer who progressed after platinum-based chemotherapy and anti-PD-(L)1 immunotherapyAn expanded cohort study was conducted. The study showed that as of March 7, 2024, out of 16 patients,31% (5 cases) of patients showed partial response (30% reduction in tumor size), and 31% (5 cases) of patients showed stable disease (tumor size change between -30% and +20%).The researchers believe that these results confirm that E7386 + lenvatinib has good preliminary anti-tumor activity and controllable safety.

According to the Eisai official website, E7386 is in Phase 1/2 clinical research internationally, being developed for monotherapy in solid tumors, combination therapy with pembrolizumab for solid tumors, and combination therapy with lenvatinib for solid tumors. The recent approval of this drug for clinical trials in China indicates that it is about to enter the clinical research phase in China.

References:

[1]Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Dec 4, 2024, fromhttps://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]Eisai to Present E7386, co-created by PRISM BioLab and Eisai, at the ESMO (European Society for Medical Oncology) Annual Meeting. Retrieved Sep 8，2024, from https://www.prnewswire.com/news-releases/eisai-to-present-e7386-co-created-by-prism-biolab-and-eisai-at-the-esmo-european-society-for-medical-oncology-annual-meeting-302241213.html

[3]The CREB-binding protein (CBP)/β-catenin inhibitor E7386, co-created by Eisai and PRISM BioLab, achieved the clinical POC (Proof of Concept). Retrieved Nov 1，2021, from https://www.eisai.com/news/2021/news202181.html

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