FDA Accepts sBLA of Trastuzumab Deruxtecan for Treatment of Individuals With HER2-Low Breast Cancer


Trastuzumab deruxtecan is an engineered HER2-directed antibody drug conjugate being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

The FDA has accepted a supplemental biologics license application (sBLA) of trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) for the treatment of adult patients who have unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer and have received a prior therapy in the metastatic setting.

Trastuzumab deruxtecan is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, which are 2 FDA initiatives that are designed to bring safe and effective cancer treatment to patients as early as possible.

“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 2 decades, only patients with HER2-positive breast cancer have been able to benefit from HER2-targeted therapies. If approved, [trastuzumab deruxtecan] 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,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said in a statement.

RTOR allows the FDA to review components of an application before submission of the completed application while Project Orbis provides a framework for concurrent submission and review of oncology medications among participating international partners. Additionally, the application has been granted priority review from the FDA.

The FDA grants priority review to applications for medicines that, if approved, would provide significant improvements over current available options by demonstrating safety or efficacy improvements, preventing a serious condition, or enhancing patient compliance.

The Prescription Drug User Fee Act date is during the fourth quarter of 2022.

The sBLA is based on date from the DENSITY-Breast04 phase 3 trial that was presented at the presidential plenary session of the 2022 American Society of Clinical Oncology Annual Meeting. The findings were published in the New England Journal of Medicine.

In the trial, trastuzumab deruxtecan demonstrated superior and clinically meaningful efficacy in both progression-free survival and overall survival in those who were previously treated and had HER2-low metastatic breast cancer with hormone receptor (HR)-positive or HR-negative disease compared to the standard of care chemotherapy.

The safety profile of trastuzumab deruxtecan was consistent with previous clinical trials with no new safety concerns identified. The interstitial lung disease or pneumonitis rates were consistent with those observed in late-line HER2-positive breast cancer trials of the drug.

“The results seen in the DESTINY-Breast04 trial represent a significant advance and reinforce the potential for [trastuzumab deruxtecan] to become a new standard of care for patients with previously treated HER2-low metastatic breast cancer,” Ken Takeshita, global head of Research and Development of Daiichi Sankyo, said in a statement.

Regulatory reviews for trastuzumab deruxtecan in the HER2-low population are also underway in the European Union and Japan.


Enhertu granted Priority Review in the US for patients with HER2-low metastatic breast cancer. News release. AstraZeneca. July 25, 2022. Accessed July 25, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-granted-priority-review-for-her2-low-mbc.html

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