Daiichi Sankyo Company, Limited announced plans to accelerate filing of the Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), in patients with HER2 positive metastatic breast cancer previously treated with ado trastuzumab emtansine (T-DM1). Submission of the application, which was originally planned for 2020, is now scheduled for the first half of fiscal year 2019.
“We are pleased to confirm the acceleration of the [fam-] trastuzumab deruxtecan clinical development program for this potential indication in patients with HER2 positive metastatic breast cancer pretreated with T-DM1 ahead of schedule,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “Simultaneously, we are committed to our aggressive development strategy evaluating the potential of [fam-] trastuzumab deruxtecan across a spectrum of HER2 expressing cancers including breast, gastric, lung and colorectal.”
[Fam-] trastuzumab deruxtecan has been granted U.S. FDA Breakthrough Therapy for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1. The initial BLA submission of [fam-] trastuzumab deruxtecan will be based on results from the pivotal phase 2 DESTINY-Breast01 study, which will be presented at an upcoming medical conference. Final determination of exact timing of the BLA submission of [fam-] trastuzumab deruxtecan will be based on the outcome of a pre-BLA meeting with the FDA.
Under the terms of the agreement, AstraZeneca will pay Daiichi Sankyo an upfront payment of $1.35 billion. Contingent payments of up to $5.55 billion include $3.8 billion for achievement of future regulatory milestones and other contingencies, as well as sales-related milestones of up to $1.75 billion. Total payments under the agreement have the potential to reach up to $6.90 billion. Daiichi Sankyo and AstraZeneca will share equally development and commercialization costs as well as profits from [fam-] trastuzumab deruxtecan worldwide, except for Japan. Daiichi Sankyo is expected to book sales in U.S., certain countries in Europe, and certain other markets where Daiichi Sankyo has affiliates. AstraZeneca is expected to book sales in all other markets worldwide, including China, Australia, Canada and Russia. The impact on Daiichi Sankyo’s consolidated results for the fiscal year ending March 31, 2019 is immaterial because the upfront payment will be booked in revenue over the period in which Daiichi Sankyo has contractual performance obligations under this collaboration. The collaboration is expected to contribute to enhancing the corporate and shareholder value of Daiichi Sankyo over the medium to long term.
About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia including five pivotal studies. [Fam-] trastuzumab deruxtecan is in pivotal phase 3 development in previously treated HER2 low expressing metastatic breast cancer versus investigator’s choice (DESTINY-Breast04); phase 3 development in HER2 positive metastatic breast cancer versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03); and phase 3 development in HER2 positive metastatic breast cancer versus investigator’s choice post T-DM1 (DESTINY-Breast02). [Fam-] trastuzumab deruxtecan also is in pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer. [Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan 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). [Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.