Daiichi Sankyo has taken a significant step forward in expanding treatment options for early-stage breast cancer patients by submitting a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for Enhertu (trastuzumab deruxtecan) as an adjuvant therapy. As reported by PharmaBiz.com, the submission targets a critical patient population: those with HER2 positive early breast cancer who still have residual invasive disease following neoadjuvant treatment.
This regulatory milestone is particularly meaningful because it addresses a substantial clinical gap. While neoadjuvant therapy aims to shrink tumors before surgery, approximately half of patients fail to achieve pathologic complete response (pCR), the ideal treatment outcome. These patients face significantly elevated recurrence risks despite receiving additional post-treatment interventions, making the need for innovative therapeutic solutions increasingly urgent.
The submission is grounded in compelling clinical evidence from the DESTINY-Breast05 phase 3 trial, which enrolled 1,635 patients across multiple continents. Results, presented at the 2025 European Society of Medical Oncology Congress and published in The New England Journal of Medicine, demonstrated that Enhertu achieved statistically significant and clinically meaningful improvements in invasive disease-free survival (IDFS) compared to trastuzumab emtansine (T-DM1), the current standard of care in this setting.
Enhertu represents an innovative advancement in cancer treatment through its unique antibody-drug conjugate (ADC) design. The medication combines a HER2-directed monoclonal antibody with multiple topoisomerase I inhibitor payloads (DXd), engineered using Daiichi Sankyo’s proprietary DXd ADC Technology. This sophisticated mechanism allows the drug to specifically target HER2 positive cancer cells while delivering potent cytotoxic agents directly to tumor sites.
The clinical rationale for this submission is reinforced by the burden of HER2 positive breast cancer. Approximately one in five breast cancer cases exhibit HER2 positivity, characterized by aggressive disease behavior and poor prognosis due to excessive growth-promoting protein expression. In Japan specifically, breast cancer ranks as the most common malignancy in women, with approximately 92,000 cases and 17,600 deaths recorded in 2022 alone.
The adjuvant setting represents a critical therapeutic opportunity. The dramatic difference in survival outcomes, from nearly 90% five-year survival in early-stage disease to approximately 30% once metastatic disease develops, underscores the importance of preventing progression in high-risk early-stage patients. By intervening after neoadjuvant therapy in patients with residual disease, Enhertu offers the potential to significantly reduce recurrence rates and improve long-term survival.
Daiichi Sankyo’s commitment extends beyond Japan. The drug has already received Breakthrough Therapy Designation from the U.S. FDA, and regulatory submissions are under review in the European Union. Additionally, the company has two other sNDAs pending in Japan for Enhertu’s use in metastatic settings, further expanding its potential clinical applications.
Currently, Enhertu is approved in more than 90 countries worldwide for treating advanced HER2 positive breast cancer and has demonstrated efficacy across multiple cancer types, including gastric cancer and non-small cell lung cancer. This Japanese submission for the adjuvant setting represents another important expansion of Enhertu’s therapeutic potential, offering hope to patients with early-stage disease who require more effective treatment options to prevent devastating recurrence.
