FDA Grants Priority Review to Enhertu for HER2-Low and -Ultralow Breast Cancer

The FDA has granted priority review to Enhertu for the potential treatment of HER2-low and HER2-ultralow breast cancer.

The Food and Drug Administration (FDA) has accepted and granted priority review to a supplemental biologics license application for Enhertu (trastuzumab deruxtecan) to treat patients with unresectable or metastatic HER2-low or -ultralow breast cancer treated with at least one endocrine therapy in the metastatic setting.

HER2-low and HER2-ultralow refer to tumors with low levels of the HER2 protein on cancer cells. According to the National Cancer Institute, HER2-low breast cancer is typically treated like HER2-negative breast cancer since cancer cells do not product enough of the HER2 protein for drugs that target HER2 to be effective.

According to a press release issued by Astra Zeneca and Daiichi Sankyo, priority review is granted by the FDA to applications for medicines that, if approved, would be an improvement to currently available treatment options for a given disease.

A drug manufacturer submits a supplemental biologics license application to request permission from the FDA to modify an existing biologics license without going through the entire drug development and approval process again. Enhertu was approved by the FDA in 2022 to treat patients with unresectable or metastatic HER2-low breast cancer.

“This priority review highlights the potential to expand the existing indication of Enhertu in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow,” Ken Takeshita, Global Head of R&D for Daiichi Sankyo, said in the release.

The supplemental biologics license application is based of findings from the DESTINY-Breast06 trial that were presented earlier this year at the 2024 American Society of Clinical Oncology Annual Meeting. In this phase 3 trial, patients treated with Enhertu had a 37% lower risk for disease progression or death compared with chemotherapy. The median progression-free survival (the time patients live after treatment without their disease worsening) was 13.2 months in patients treated with Enhertu compared with 8.1 months in those treated with chemotherapy.

Results from the DESTINY-Breast06 trial were consistent between patients with HER2-low and HER2-ultralow expressions. The median PFS for patients with HER2-low breast cancer treated with Enhertu was 13.2 months compared with 8.1 months in those treated with chemotherapy. For patients with HER2-ultralow breast cancer, the respective median PFS were 13.2 months and 8.3 months.

“While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is associated with poor response rates and outcomes,” Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, said in a press release. “The results from DESTINY-Breast06 show that Enhertu has the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.”

Enhertu is an antibody-drug conjugate directed towards HER2. According to the National Cancer Institute, an antibody-drug conjugate is a substance that consists of a monoclonal antibody that is chemically linked to a drug. In this case, the monoclonal antibody connects to the HER2 protein on cancer cells, and the linked drug enters these cells to kill them without posing harm to other cells.

Enhertu also received breakthrough therapy designation for the treatment of HER2-low and HER2-ultralow breast cancer in August 2024. According to the FDA, breakthrough therapy designations are intended to speed up the development and potential approval of drugs that treat serious conditions or diseases.

The FDA designated a Prescription Drug User Fee Act date in the first quarter of 2025, meaning that the agency will need to make its decision on the application in the first three months of 2025.

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