Daiichi Sankyo And AstraZeneca's Breast Cancer Drug ENHERTU Accepted For FDA Review In Early-Stage HER2 Patients

Daiichi Sankyo (TSE: 4568) and AstraZeneca's (NASDAQ:AZN) supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) followed by paclitaxel, trastuzumab and pertuzumab (THP) has been accepted for review in the U.S. for the neoadjuvant treatment of adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer.

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The acceptance is based on results from the DESTINY-Breast11 phase 3 trial, which showed that ENHERTU followed by THP demonstrated a statistically significant and clinically meaningful improvement in pathologic compete response (pCR) rate along with an improved safety profile compared to dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used prior to surgery for patients with high-risk, locally advanced HER2 positive early-stage breast cancer. Data from the trial also showed an early positive trend in event-free survival (EFS) favoring ENHERTU followed by THP compared to ddAC-THP. The Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their regulatory decision, is May 18, 2026.

Approximately one in three patients with early-stage breast cancer are considered high-risk, meaning they are more likely to experience disease recurrence and have a poor prognosis.1,2 Achieving pCR in early-stage HER2 positive breast cancer, defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment, is associated with improved long-term outcomes.3,4 Currently, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the unmet medical need for new treatment options.2,5 The current standard of care in this neoadjuvant setting varies across regions but generally consists of combination chemotherapy regimens.

"Achieving a pathologic complete response prior to surgery in HER2 positive early-stage breast cancer is critical to reducing the risk of disease recurrence and improving the potential for cure," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "If approved, ENHERTU could change how patients with high-risk HER2 positive early-stage breast cancer are treated and we look forward to working closely with the FDA to bring this innovative treatment regimen to patients in this setting."

"The clinically meaningful improvement in pathologic complete response and favorable safety profile seen with DESTINY-Breast11 highlight the opportunity for ENHERTU followed by THP to become an important new approach for patients with HER2 positive early breast cancer," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "ENHERTU is already established in the metastatic setting and now we have the potential to expand its use into earlier stages of disease where cure is possible."

In DESTINY-Breast11, ENHERTU followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of ENHERTU and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the ENHERTU followed by THP and the ddAC-THP arms as determined by an independent adjudication committee.

Following a recommendation by the Independent Data Monitoring Committee, patient enrollment in a third arm of DESTINY-Breast11 evaluating ENHERTU alone was closed based on a previous efficacy assessment of the study arms.

ENHERTU has demonstrated improved outcomes in six phase 3 breast cancer trials across different subtypes and stages of disease, including data from the DESTINY-Breast09 phase 3 trial, which were recently presented at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting and granted Priority Review in the U.S., evaluating ENHERTU in the first-line HER2 positive metastatic setting, as well as positive topline results from a planned interim analysis of the DESTINY-Breast05 phase 3 trial evaluating ENHERTU versus trastuzumab emtansine (T-DM1) in patients with HER2 positive early breast cancer with residual invasive disease in the breast or axillary lymph nodes after neoadjuvant treatment and high risk of disease recurrence. Data from DESTINY-Breast11 (Abstract #291O) and DESTINY-Breast05 (Abstract #LBA1) will be presented during Presidential Symposium I on Saturday, October 18 at the upcoming 2025 European Society for Medical Oncology (#ESMO25) Congress.