DS-8201, an investigational HER2-targeting antibody-drug conjugate or ADC being developed by Daiichi Sankyo, has received SAKIGAKE Designation for the treatment of HER2-positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).
DS-8201, also known as trastuzumab deruxtecan, is Daiichi Sankyo’s lead product in the company’s investigational ADC Franchise.
Antibody-drug Conjugates are targeted agents being developed for the treatment of cancer that deliver cytotoxic chemotherapy payload directly to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201, a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.
DS-8201 is currently in pivotal phase II clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1, also known as ado-trastuzumab emtansine (DESTINY-Breast01), pivotal phase II development for HER2-positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01), phase 2 development in advanced colorectal cancer and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.
“There are no HER2-targeting treatment options currently available for patients with HER2-positive gastric cancer whose tumors are no longer controlled by trastuzumab,” said Koichi Akahane, Ph.D, MBA, Executive Officer, Head of Oncology Function, R&D Division, Daiichi Sankyo.
“We look forward to working closely with the Japan Ministry of Health, Labour and Welfare under the terms of the SAKIGAKE program to accelerate the development of DS-8201 particularly since Japan has one of the highest incidence rates of gastric cancer worldwide,” Akahane added
The SAKIGAKE Designation System promotes Research & Development in Japan, driving early practical application for innovative pharmaceutical products, medical devices and regenerative medicines.
As a designated medicine under the SAKIGAKE Designation system, DS-8201 will have prioritized consultation, a dedicated review system to support the development and review process, as well as reduced review time from the normal 12 to 6 months.
Breakthrough Therapy and Fast Track
“We are pleased that DS-8201 has received SAKIGAKE Designation for advanced HER2-positive gastric cancer, which follows the Breakthrough Therapy and Fast Track designations granted by the U.S. FDA for HER2-positive metastatic breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo.
“These three designations for DS-8201 underscore our commitment to active and close collaborations with health authorities in order to potentially bring DS-8201 as a new treatment option to patients with different types of HER2-expressing cancers worldwide as quickly as possible,” Yver added.
SAKIGAKE Designation was granted based on the results of an ongoing phase 1 study assessing the safety, tolerability and preliminary efficacy of DS-8201. Updated preliminary results of DS-8201 from a subgroup analysis of HER2-positive advanced gastric cancer previously treated with trastuzumab and chemotherapy were recently presented at the 2018 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
Unmet Need in Gastric Cancer
Gastric cancer is the fifth most common cancer worldwide, with nearly one million new cases reported in 2012. Approximately half of all gastric cancer cases occur in eastern Asia, with Japan having the third highest incidence rate worldwide. Gastric cancer is the third leading cause of cancer-related death worldwide, and the second leading cause of cancer-related death in Japan. 
Approximately one in five gastric cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells. HER2-expressing gastric cancer is an area of unmet medical need as advances in the treatment of the disease have been limited, largely due to its genetic complexity and heterogeneity.  Currently, there are no approved HER2-targeting therapy options for patients with HER2-positive advanced gastric cancer after treatment with trastuzumab.