EMA Validates ENHERTU® for HER2 Low/Ultralow Metastatic Breast Cancer Post-Endocrine Therapy

TOKYO, Japan & MUNICH, Germany I August 19, 2024 I Daiichi Sankyo (TSE: 4568) has announced that the European Medicines Agency (EMA) has validated the Type II Variation application for ENHERTU® (trastuzumab deruxtecan). This application seeks approval for ENHERTU as a monotherapy for treating 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.

ENHERTU is a HER2 directed DXd antibody drug conjugate (ADC) created by Daiichi Sankyo and is being co-developed and commercialized with AstraZeneca (LSE/STO/Nasdaq: AZN). The validation from the EMA confirms that the application is complete, enabling the commencement of a scientific review by the EMA’s Committee for Medicinal Products for Human Use. This submission is supported by data from the DESTINY-Breast06 phase 3 trial, presented at the 2024 American Society of Clinical Oncology Annual Meeting.

“This submission builds on our existing indication for ENHERTU in patients with HER2 low metastatic breast cancer and an expanded approval would enable the potential for use in an earlier disease setting as well as in a broader patient population that now includes HER2 ultralow,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We look forward to working closely with the EMA to potentially bring this medicine to more patients in the EU.”

Additional regulatory submissions for ENHERTU in this indication are in progress worldwide.

About DESTINY-Breast06

DESTINY-Breast06 is an extensive, global, randomized, open-label phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) compared to the investigator’s choice of chemotherapy (capecitabine, paclitaxel, or nab paclitaxel) in patients with HR positive, HER2 low or HER2 ultralow advanced or metastatic breast cancer. Participants had not been previously treated with chemotherapy for advanced or metastatic disease but had received at least two lines of prior endocrine therapy in the metastatic setting. Some patients had also received a combination of endocrine therapy with a CDK4/6 inhibitor and experienced disease progression within six months of starting treatment or experienced disease recurrence within 24 months of adjuvant treatment.

The primary endpoint of the trial is progression-free survival (PFS) in the HR positive, HER2 low patient population as determined by blinded independent central review (BICR). Secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in the HER2 low patient population, and OS in the overall trial population. Other secondary endpoints involve objective response rate, duration of response, time to first and second subsequent treatment or death, and safety. The analysis of the HER2 ultralow subgroup was not designed to demonstrate statistical significance.

DESTINY-Breast06 enrolled 866 patients across multiple regions including Asia, Europe, North America, Oceania, and South America.

About Breast Cancer and HER2 Expression

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths globally. In 2022, over two million breast cancer cases were diagnosed, resulting in more than 665,000 deaths worldwide. In Europe alone, approximately 557,000 cases are diagnosed annually. While survival rates are high for early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to survive five years post-diagnosis.

HER2 is a protein expressed on the surface of various tumor types, including breast cancer. Patients with high HER2 expression are categorized as HER2 positive and are treated with targeted therapies, representing about 15% to 20% of breast cancer cases. Historically, tumors not classified as HER2 positive were considered HER2 negative, although many still have some level of HER2 expression. Approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low, and potentially an additional 25% may be HER2 ultralow.

Endocrine therapies are prevalent in the early stages of treatment for HR positive metastatic breast cancer. However, the efficacy of further endocrine treatments diminishes after two lines of therapy. Consequently, the current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved for patients with HER2 low expression. Currently, no targeted therapies are specifically approved for HER2 ultralow expression.

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