Following the news that AstraZeneca has entered into a global development and commercialization agreement for Daiichi Sankyo’s trastuzumab deruxtecan (DS-8201), a proprietary antibody-drug conjugate (ADC) and potential new targeted medicine for cancer treatment,

Tajekesa Chapman, Oncology and Hematology Analyst at GlobalData, offers her view on the deal:

“Trastuzumab deruxtecan shows great promise for the treatment of multiple HER2-expressing cancers, such as breast, colorectal, gastric, and non-small cell lung cancer, as well as patients with clinically low HER2 expression (HER2-low). Coming in at $6.9bn, the deal is carefully structured to minimize risk with an initial funding of $3.5bn within the first 12 months, of which $1.35bn will be paid up front. The agreement will see the two companies sharing global profits for the anticipated blockbuster in all countries excluding Japan, where Daiichi Sankyo will retain exclusive rights. AstraZeneca expects significant contributions from trastuzumab deruxtecan in 2023, and Daiichi Sankyo expects the ADC to contribute to the bulk of its target annual sales of over $4.5bn from its oncology treatment portfolio by 2025.

“HER2 is a tyrosine kinase receptor and growth-promoting protein overexpressed in 20–30% of invasive breast cancers. It has been the primary target in approved therapies such as Roche’s monoclonal antibodies, Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab emtansine, T-DM1), and Novartis’ tyrosine kinase inhibitor Tykerb (lapatinib). Despite this saturation in the market, there are several unmet needs remaining, including those relating to severe side effects, treatment failure, and drug resistance.

“Trastuzumab deruxtecan is in late stage development, currently undergoing the pivotal Phase III DESTINY-Breast02 and DESTINY-Breast03 trials for the third- and second-line treatment of HER2-positive metastatic breast cancer, respectively. DESTINY-Breast03 is a head-to-head trial with Kadcyla, which is also a HER2-targeting ADC. This trial could prove to be a potential game-changer for AstraZeneca and Daiichi Sankyo, with the potential to alter the treatment paradigm and emerge as a standard of care treatment.

“GlobalData expects that trastuzumab deruxtecan will enter a competitive HER2-positive breast cancer market, growing to $10bn by 2025 in the eight major markets (8MM). While Roche has previously pioneered in this market, its patent expiry of Herceptin in the five major European markets (5EU) and Japan in 2014, and in the US in 2019, has allowed the entry of biosimilar trastuzumab into the HER2-positive breast cancer market, negatively impacting the overall market as Herceptin sales are eroded by biosimilar competition. Daiichi Sankyo now expects to file its FDA application for trastuzumab deruxtecan in breast cancer treatment starting from this year, posing direct competition to Kadcyla and positioning itself as a downstream threat to Roche’s HER2-targeting trio.”

* 8MM: The US, France, Germany, Italy, Spain, the UK, Japan, China

* 5EU: France, Germany, Italy, Spain and the UK