Daiichi Sankyo and AstraZeneca announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to the supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) in combination with pertuzumab. The application seeks approval of the regimen as a first-line treatment for adult patients with unresectable or metastatic HER2 positive breast cancer.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca.
Priority Review is reserved for medicines that, if approved, could deliver significant improvements in safety, efficacy, or patient outcomes. The designation follows the Breakthrough Therapy Designation granted earlier in 2025 for ENHERTU plus pertuzumab, based on the pivotal phase 3 DESTINY-Breast09 trial. The FDA’s target action date under the Prescription Drug User Fee Act (PDUFA) is January 23, 2026.
The application is also being reviewed under the Real-Time Oncology Review (RTOR) program, an FDA initiative that accelerates access to promising therapies by allowing regulators to assess parts of an application before the full submission.
Findings from DESTINY-Breast09, presented as a late-breaking oral session at the 2025 ASCO Annual Meeting, showed that ENHERTU in combination with pertuzumab reduced the risk of disease progression or death by 44% compared to the current standard regimen of taxane, trastuzumab, and pertuzumab (THP) (HR: 0.56; 95% CI: 0.44-0.71; p<0.00001).
Median progression-free survival (PFS) with the ENHERTU regimen was 40.7 months versus 26.9 months with THP, as assessed by blinded independent central review. Confirmed objective response rate (ORR) was 85.1% with ENHERTU plus pertuzumab compared with 78.6% for THP. Median duration of response exceeded three years (39.2 months) for ENHERTU plus pertuzumab compared to 26.4 months with THP.
“ENHERTU in combination with pertuzumab delayed disease progression for more than three years compared to around two years with current standard of care as a first-line treatment for patients with HER2 positive metastatic breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Receiving Priority Review moves us closer to offering ENHERTU to patients even earlier in the metastatic treatment pathway as a potential new first-line treatment option.”
“The DESTINY-Breast09 trial showed that treating patients with HER2 positive metastatic breast cancer with ENHERTU in combination with pertuzumab until progression in the first-line setting produced a new landmark of more than 40 months for progression-free survival and nearly doubled the number of patients with no evidence of disease on imaging,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “This marks the first major evolution in treatment in this first-line setting in more than a decade – a setting where a strong response is crucial, as up to one third of patients may not receive second-line therapy.”
ENHERTU is already approved in over 85 countries for patients with previously treated HER2 positive breast cancer, based on results from the DESTINY-Breast03 trial. The FDA’s Priority Review for ENHERTU plus pertuzumab brings the possibility of introducing this treatment earlier in the care pathway, potentially transforming outcomes for patients with HER2 positive metastatic breast cancer.