A drug candidate for unresectable or metastatic breast cancer has been accepted by the US Food and Drug Administration (FDA).
The drug is being jointly developed and commercialized and the result of a high-profile partnership between AstraZeneca and Daiichi Sankyo.
Enhertu (trastuzumab deruxtecan) is a specifically engineered HER2-directed antibody drug conjugate (ADC).
The companies received notification of the acceptance of their supplemental Biologics License Application (sBLA) for Enhertu, on Monday (July 26).
The sBLA is based on data from the DESTINY-Breast04 Phase III trial that were presented at the presidential plenary session of the 2022 American Society of Clinical Oncology Annual Meeting and simultaneously published in The New England Journal of Medicine.
Enhertu was designed to treat unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridization [ISH]-negative) breast cancer patients who have received a prior therapy in the metastatic setting. The application has been granted Priority Review by the FDA and the outcome is expected to come out with a regulatory decision later this year.
Phase 3 trial
Data from the phase 3 DESTINY-Breast04 trial formed the core of Enhertu’s sBLA. The trial enrolled more than 550 patients with low HER2 levels. Compared with physician-chosen chemotherapy, treatment with Enhertu led to significantly longer progression-free and overall survival. The drug candidate also proved to be as safe and tolerable as existing chemotherapies.
Susan Galbraith, executive vice president, oncology research and development at AstraZeneca, said: “The data from DESTINY-Breast04 represent the first time a HER2-targeted therapy has shown a survival benefit in patients with HER2-low metastatic breast cancer. For more than two decades, only patients with HER2-positive breast cancer have been able to benefit from HER2-targeted therapies. If approved, Enhertu will redefine how we classify and treat metastatic breast cancer, enabling patients whose tumors have lower levels of HER2 expression the opportunity to benefit from a HER2-directed therapy.”
Priority Review is given by the FDA to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.
New standard of care
Ken Takeshita, global head, research and development, at Daiichi Sankyo, said: “The results seen in the DESTINY-Breast04 trial represent a significant advance and reinforce the potential for Enhertu to become a new standard of care for patients with previously treated HER2-low metastatic breast cancer. The prioritization of this application by the FDA supports the importance of these data, and we look forward to working with the FDA to potentially bring Enhertu to patients with HER2-low metastatic breast cancer as quickly as possible.”
In the trial, Enhertu demonstrated clinically meaningful efficacy in progression-free survival (PFS) and overall survival (OS) in previously treated patients with HER2-low metastatic breast cancer with hormone receptor (HR)-positive or HR-negative disease versus standard of care physician’s choice of chemotherapy.
The safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified. Interstitial lung disease or pneumonitis rates were consistent with that observed in late-line HER2-positive breast cancer trials of Enhertu, as determined by an independent adjudication committee.