ENHERTU® gets US Priority Review for HER2-low/ultralow metastatic breast cancer post-endocrine therapy

AstraZeneca and Daiichi Sankyo have announced that their supplemental Biologics License Application (sBLA) for ENHERTU (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review by the U.S. Food and Drug Administration (FDA). This application seeks approval 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. This decision is based on positive results from the DESTINY-Breast06 Phase III trial, which demonstrated significant benefits of ENHERTU over chemotherapy in terms of progression-free survival.

ENHERTU is poised to become the first HER2-directed therapy and antibody-drug conjugate (ADC) available for these patients prior to chemotherapy. Additionally, the FDA has recently granted ENHERTU Breakthrough Therapy Designation for this patient group, expediting its development and regulatory review due to its potential to address unmet medical needs.

Breast cancer subtypes are typically classified based on hormone receptor (HR) and HER2 status. HR-positive, HER2-negative breast cancer accounts for approximately 70% of all cases. Research indicates that many of these tumors exhibit some level of HER2 expression, with up to 90% being classified as HER2-low or HER2-ultralow.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, noted that while endocrine therapies are commonly used initially for HR-positive metastatic breast cancer, their benefits diminish with subsequent treatments, often leading to poor outcomes with chemotherapy. The DESTINY-Breast06 trial results suggest that ENHERTU could revolutionize treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.

Ken Takeshita, Global Head of R&D at Daiichi Sankyo, emphasized the importance of the Priority Review status, which could expand the current indication of ENHERTU to earlier stages of the disease and a wider patient population, including those with HER2-ultralow expression.

Data from the DESTINY-Breast06 trial, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine, revealed that ENHERTU reduced the risk of disease progression or death by 37% compared to chemotherapy in the overall trial population. Specifically, the median progression-free survival (PFS) was 13.2 months for ENHERTU versus 8.1 months for chemotherapy. Consistent results were observed across both HER2-low and HER2-ultralow subgroups.

The safety profile of ENHERTU in the trial was consistent with previous studies, with no new safety issues identified. ENHERTU, an engineered HER2-directed DXd ADC, was co-developed by Daiichi Sankyo and AstraZeneca and is already approved in over 65 countries for patients with HER2-low metastatic breast cancer who have previously undergone systemic therapy.

The ongoing development program for ENHERTU encompasses multiple HER2-targetable cancers, with several clinical trials assessing its efficacy as a monotherapy and in combination with other treatments.

AstraZeneca and Daiichi Sankyo's collaboration on ENHERTU began in March 2019, with both companies jointly developing and commercializing the drug worldwide, excluding Japan where Daiichi Sankyo retains exclusive rights. The partnership aims to leverage their combined expertise to bring innovative cancer treatments to patients globally.

AstraZeneca is committed to transforming cancer care, with a robust pipeline of treatments aiming to redefine how breast cancer is classified and treated. Their efforts include advancing treatments for HR-positive breast cancer and exploring the potential of various targeted therapies and combinations, all with the ultimate goal of eliminating cancer as a cause of death.

Overall, the acceptance and Priority Review of the sBLA for ENHERTU mark significant progress in the treatment landscape for metastatic breast cancer, potentially offering a new, more effective treatment option for patients with HER2-low and HER2-ultralow disease.