AstraZeneca and Daiichi Sankyo Submit New Clinical Trial Application in China for HER2-Targeted ADC Enhertu (DS-8201)

On October 14, the latest public notice on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration indicated that Daiichi Sankyo had submitted a new clinical trial application in China for the antibody-drug conjugate Enhertu (DS-8201). This HER2-targeted ADC therapy is a key development project jointly pursued by AstraZeneca and Daiichi Sankyo, with a collaboration deal valued at up to $6.9 billion.

Source: CDE Official Website

Since the beginning of this year, Enhertu has achieved multiple milestones: several clinical results in gastric cancer, colorectal cancer, and lung cancer were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting; it received its third Breakthrough Therapy Designation from the U.S. FDA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring HER2 mutations; and it gained approval in Japan for a new indication to treat patients with unresectable advanced or recurrent HER2-positive gastric cancer.

Enhertu is a HER2-targeting antibody-drug conjugate (ADC) that leverages Daiichi Sankyo’s proprietary ADC technology. It links trastuzumab, a humanized HER2 antibody, to a novel topoisomerase I inhibitor via a tetrapeptide linker, thereby targeting cancer cells and delivering the drug intracellularly. Compared with conventional chemotherapy, this class of novel agents can reduce the toxic side effects associated with chemotherapeutic drugs.

Enhertu has long attracted significant attention during its development. It was listed by EvaluatePharma as one of the top 10 potential blockbuster drugs for 2024. In March 2019, AstraZeneca invested $6.9 billion to partner with Daiichi Sankyo for the global co-development and commercialization of Enhertu. The drug has also received three Breakthrough Therapy Designations from the U.S. FDA for the treatment of patients with HER2-positive breast cancer, gastric cancer, and non-small cell lung cancer (NSCLC).

In late 2019, Enhertu received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who had previously received two or more anti-HER2 regimens. This September, the product’s expanded indication was approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with unresectable, advanced or recurrent HER2-positive gastric cancer.

In China, according to information from the CDE official website, DS-8201a was first submitted for clinical trial approval and accepted in November 2018. Currently, multiple clinical trial applications for this product have been submitted in China, among which three have received implicit approval for clinical trials. The intended indications for development include:

· Unresectable/metastatic breast cancer with human epidermal growth factor receptor 2 (HER2) positive expression;

· Unresectable and/or metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2);

· Patients with HER2-low, hormone receptor (HR)-positive advanced or metastatic breast cancer who have experienced disease progression following endocrine therapy.

According to the Chinese Drug Clinical Trial Registration and Information Publicity Platform, a Phase 3, multicenter, randomized, open-label, active-controlled trial comparing the novel targeted therapy DS-8201a with physician’s choice of treatment in patients with HER2-low advanced breast cancer is currently underway.

According to public information, AstraZeneca and Daiichi Sankyo plan to launch more than 40 clinical trials to explore the efficacy of Enhertu in treating HER2-low breast cancer, as well as HER2-positive lung cancer, gastric cancer, colorectal cancer, and tumor-agnostic indications. The submission of a new clinical trial application for this product in China also means that it is expected to conduct clinical trials for more indications in China.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Oct 14, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] ENHERTU® Approved in Japan for the Treatment of Patients with HER2 Positive Metastatic Gastric Cancer. Retrieved September 25, 2020, from https://www.businesswire.com/news/home/20200925005163/en

[3] ENHERTU Granted Breakthrough Therapy Designation in the US for HER2-Mutant Metastatic Non-Small Cell Lung Cancer. Retrieved 2020-05-18, from https://www.businesswire.com/news/home/20200518005160/en/ENHERTU-Granted-Breakthrough-Therapy-Designation-HER2-Mutant-Metastatic

Source: Medical Panorama

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