The supplemental Biologics License Application – sBLA for Enhertu – trastuzumab deruxtecan by AstraZeneca and Daiichi Sankyo has been accepted as well as granted Priority Review in the U.S. when it comes to the treatment of adult patients with HER2‑positive early breast cancer who happen to have residual invasive disease after neoadjuvant HER2‑targeted therapy.
Enhertu Priority Review is granted by the USFDA and is reserved for medicines that could significantly improve existing treatment options, either through enhanced efficacy, safety, or patient compliance. The FDA’s regulatory decision is expected in the third quarter of 2026 under the Prescription Drug User Fee Act timeline.
Enhertu has also in the past received Breakthrough Therapy Designation – BTD in this setting by the FDA, which accelerates development and review for therapies addressing serious conditions with unmet medical needs. Additionally, the sBLA is being reviewed under Project Orbis, which is a collaborative framework that allows concurrent submission and evaluation of oncology medicines among international partners.
It is well to be noted that HER2‑positive breast cancer accounts for about one in five breast cancers and is often aggressive with poor prognosis. Approximately half of patients with HER2‑positive early breast cancer have residual disease after neoadjuvant treatment, which increases the risk of recurrence. Even with current post‑neoadjuvant therapies, many patients still progress to metastatic disease, where the 5-year survival rates drop sharply from nearly 90% to around 30%.
The executive vice president of oncology hematology R&D with AstraZeneca, Susan Galbraith, 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.”
The Global Head, R&D, Daiichi Sankyo, Ken Takeshita, 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. Enhertu 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 submission is supported by data from the Phase III DESTINY‑Breast05 trial, which was presented at the European Society for Medical Oncology – ESMO 2025 Congress and published in The New England Journal of Medicine. In this study, Enhertu significantly went on to reduce the risk of invasive disease recurrence or death by 53% compared to trastuzumab emtansine, having a hazard ratio of 0.47. The three-year IDFS rate was 92.4% for Enhertu as against 83.7% for T‑DM1. IDFC results were consistent across all prespecified subgroups. Enhertu also reduced the risk of disease recurrence or death by 53%, lowered distant recurrence risk by 51%, and reduced brain metastasis risk by 36% compared with T‑DM1. Importantly, the safety profile was pretty consistent with prior data, with no new concerns identified.
Regulatory submissions, which are based on DESTINY‑Breast05, are also under review in the EU and Japan. In parallel, another sBLA is under FDA review for Enhertu combined with paclitaxel, trastuzumab, and pertuzumab – THP in the neoadjuvant setting, supported by DESTINY‑Breast11 trial data. It is well to be noted that Enhertu is already approved in over 90 countries for HER2‑positive metastatic breast cancer. The drug is a specifically engineered HER2‑directed DXd antibody‑drug conjugate – ADC, which has been discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca.
