AstraZeneca’s and Daiichi Sankyo’s Enhertu Gains Another Breakthrough Therapy Designation
The FDA has granted AstraZeneca’s and Daiichi Sankyo’s antibody drug conjugate Enhertu (trastuzumab deruxtecan) a fifth Breakthrough Therapy designation for patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer who have received certain prior treatments.
The latest designation is for patients who have received a prior systemic therapy or developed disease recurrence within six months of completing adjuvant chemotherapy.
The new designation was supported by results from a phase 3 trial in which patients given Enhertu showed a significant improvement in both progression-free survival and overall survival compared with those given the physician’s choice of chemotherapy.
The FDA first approved Enhertu in 2019 for patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma. The potential blockbuster drug has also received FDA’s accelerated approval for the treatment of unresectable or metastatic HER2-positive breast cancer.
Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan (a derivative of exatecan). It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.
It was approved for medical use in the United States in December 2019, in Japan in March 2020, in the European Union in January 2021, and in Australia in October 2021.
April 28, 2022
