AstraZeneca and Daiichi Sankyo have announced that the U.S. Food and Drug Administration (FDA) has accepted their supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) in combination with pertuzumab for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. The FDA has also granted Priority Review to the application, signaling that Enhertu could offer significant improvements over current treatment options. The FDA’s regulatory decision is expected by the first quarter of 2026.
Enhertu recently received Breakthrough Therapy Designation (BTD) from the FDA in this treatment setting, which aims to expedite the development and review of therapies addressing serious conditions with unmet medical needs. HER2-positive metastatic breast cancer is an aggressive form affecting 15% to 20% of metastatic breast cancer patients, with about 10,000 patients treated annually in the U.S. first-line setting.
Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, highlighted results from the DESTINY-Breast09 Phase III trial, which showed that the combination of Enhertu and pertuzumab achieved a median progression-free survival (PFS) of over 40 months—nearly doubling the number of patients with no evidence of disease compared to standard treatment. She noted this represents the first major advancement in first-line treatment for this patient group in over a decade.
Ken Takeshita, Global Head of R&D at Daiichi Sankyo, emphasized that the combination delayed disease progression for more than three years, compared to around two years with the current standard of care. He said the Priority Review brings the companies closer to providing patients earlier access to this potential new treatment option.
The sBLA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program, which allows for a faster and more efficient evaluation of cancer therapies by reviewing components of the application before the full submission.
Data from the DESTINY-Breast09 trial, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% compared to the standard combination of taxane, trastuzumab, and pertuzumab (THP). Median PFS was 40.7 months for the Enhertu combination versus 26.9 months for THP, with consistent benefits across patient subgroups.
The confirmed objective response rate (ORR) was 85.1% with Enhertu plus pertuzumab, compared to 78.6% with THP, including 58 complete responses versus 33 in the standard treatment group. The safety profile of the combination was consistent with known effects of the individual drugs, and no new safety concerns were identified.
Enhertu is a HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. It is currently approved in more than 85 countries as a second-line treatment for HER2-positive breast cancer, based on results from the DESTINY-Breast03 trial.