AstraZeneca and Daiichi Sankyo's supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) has been accepted and granted Priority Review in the US for the treatment of adult patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment.
The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for its regulatory decision, is anticipated during the third quarter of 2026.
Enhertu was recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.
The sBLA also is being reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners.
Around one in five breast cancers are considered HER2-positive, a subtype that is often associated with aggressive disease and poor prognosis.1-3 Currently, approximately half of patients with HER2-positive early breast cancer have residual disease following neoadjuvant treatment (before surgery), putting them at an increased risk of disease recurrence.4-9 Despite receiving additional treatment in the post-neoadjuvant setting with current standards of care, some patients still experience tumour progression to metastatic disease, where the five-year survival rate drops from nearly 90% to approximately 30%.10,11
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "While there has been significant progress in treating HER2-positive early breast cancer, managing patients at a higher risk of recurrence remains challenging. With this Priority Review, we move closer to bringing Enhertu to the post-neoadjuvant setting, offering more patients the opportunity for sustained long-term outcomes and a potential path to cure."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "For patients with residual invasive disease after neoadjuvant therapy, identifying additional treatments following surgery is critical to help further reduce the risk of recurrence and help prevent progression to metastatic disease. This Priority Review reinforces the potential of Enhertu to become a new standard of care for HER2-positive early breast cancer based on the results of DESTINY-Breast05."
The sBLA is based on data from the DESTINY-Breast05 Phase III trial presented at the European Society for Medical Oncology (ESMO) 2025 Congress and subsequently published in The New England Journal of Medicine.1
In the trial, Enhertu significantly reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53% compared with trastuzumab emtansine (T-DM1; based on a hazard ratio [HR] of 0.47; 95% confidence interval [CI] 0.34-0.66; p<0.0001) as a post-neoadjuvant treatment for patients with HER2-positive breast cancer. Enhertu demonstrated a three-year IDFS rate of 92.4% compared with 83.7% with T-DM1. IDFS findings were consistent across all prespecified subgroups.
Enhertu also significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]), a key secondary endpoint, by 53% versus T-DM1 (HR 0.47; 95% CI 0.34-0.66; p<0.0001). Further, Enhertu lowered the risk of distant disease recurrence (distant recurrence-free interval) by 51% and the risk of brain metastases (brain metastasis-free interval) by 36% compared with T-DM1 (HR 0.64; 95% CI 0.35-1.17).
The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified.
Regulatory submissions for Enhertu based upon DESTINY-Breast05 are also under review in the EU and Japan. In addition, an sBLA for Enhertu followed by paclitaxel, trastuzumab and pertuzumab (THP) currently is under review in the US for the neoadjuvant treatment of patients with HER2-positive early breast cancer based on results from the DESTINY-Breast11 trial.
Enhertu is already approved in more than 90 countries as a treatment for patients with HER2-positive metastatic breast cancer.
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Notes
Post-neoadjuvant treatment for HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.12 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.12 In the US, more than 320,000 cases of breast cancer are diagnosed annually with more than 42,000 deaths.13
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.14 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.14 Approximately one in five cases of breast cancer are considered HER2-positive.2-3
For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.9 However, approximately half of patients who receive neoadjuvant treatment do not experience pCR, putting them at increased risk of disease recurrence.4-9
Despite receiving additional treatment for residual disease in the post-neoadjuvant setting, some patients still experience invasive disease or death, and current treatment options have shown limited impact on central nervous system recurrence.11 In the US, around 16,000 patients with HER2-positive early breast cancer receive treatment in the post-neoadjuvant setting (after surgery) each year.15
DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive early breast cancer with residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.
The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomisation until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include overall survival, distant recurrence-free interval, brain metastases-free interval and safety.
