AstraZeneca and Daiichi Sankyo have announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to their supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan). This review is for the treatment of adult patients with unresectable or metastatic HER2-low or HER2-ultralow breast cancer who have undergone at least one endocrine therapy in the metastatic setting. The application is based on positive results from the Phase III DESTINY-Breast06 trial, which compared Enhertu with chemotherapy.
The FDA’s Priority Review designation is given to applications for treatments that could offer significant improvements over existing options by enhancing safety, efficacy, or patient outcomes. The Prescription Drug User Fee Act (PDUFA) target date for the FDA’s regulatory decision is anticipated in the first quarter of 2025.
Enhertu was also recently awarded Breakthrough Therapy Designation (BTD) by the FDA in this treatment setting. BTD is intended to expedite the development and review of new medicines designed to treat serious conditions and address unmet medical needs.
HR-positive, HER2-negative breast cancer is the most common subtype, accounting for about 70% of all breast cancers. Many of these tumors, though classified as HER2-negative, exhibit some level of HER2 expression. It is estimated that 85-90% of tumors classified as HR-positive, HER2-negative may actually be HER2-low or HER2-ultralow.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the potential impact of Enhertu, stating, “While endocrine therapies are often used in treating HR-positive metastatic breast cancer, their benefits are limited with additional treatments, and chemotherapy has poor outcomes. DESTINY-Breast06 shows that Enhertu could transform the current HR-positive treatment landscape and become the first targeted therapy for patients with HER2-low or HER2-ultralow expression after endocrine therapy.”
Ken Takeshita, Global Head of R&D at Daiichi Sankyo, added, “This Priority Review underscores the potential to extend Enhertu’s indication for HER2-low metastatic breast cancer to an earlier stage of the disease and include a broader population, including HER2-ultralow. We look forward to working closely with the FDA to make Enhertu available to more patients.”
The sBLA is supported by data from the DESTINY-Breast06 Phase III trial, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. In the trial, Enhertu reduced the risk of disease progression or death by 37% compared to chemotherapy. The median progression-free survival (PFS) was 13.2 months for Enhertu, versus 8.1 months for chemotherapy.
Results were consistent across both HER2-low and HER2-ultralow expression patients. Specifically, in HER2-low patients, Enhertu demonstrated a median PFS of 13.2 months compared to 8.1 months with chemotherapy. In a prespecified exploratory analysis of HER2-ultralow patients, Enhertu achieved a median PFS of 13.2 months compared to 8.3 months.
The safety profile of Enhertu in the trial was consistent with previous studies, with no new safety concerns identified.
Enhertu, a HER2-directed DXd antibody-drug conjugate, was developed by Daiichi Sankyo and is being jointly developed and marketed by AstraZeneca and Daiichi Sankyo. It is already approved in over 65 countries, including the U.S., for patients with HER2-low metastatic breast cancer who have received prior systemic therapy or experienced recurrence after adjuvant chemotherapy based on results from the DESTINY-Breast04 trial.
