As reported on PharmaBiz, the US Food and Drug Administration (FDA) has accepted and granted Priority Review to AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) as a post‑neoadjuvant therapy for adults with HER2‑positive early breast cancer who have residual invasive disease after receiving HER2‑targeted treatment before surgery. A regulatory decision is expected in the third quarter of 2026.
Why This Matters
HER2‑positive tumors account for roughly 20% of breast cancer cases and are often linked to more aggressive disease. Nearly half of patients still show residual disease after standard neoadjuvant therapy, placing them at higher risk for recurrence and progression to metastatic cancer—where survival rates fall sharply.
With its Priority Review status, Enhertu is positioned as a potentially important option for these high‑risk patients. The FDA has also granted the therapy Breakthrough Therapy Designation, underscoring its potential to address a significant unmet clinical need. The application is additionally being reviewed through Project Orbis, enabling simultaneous evaluation by global regulatory partners.
Key Findings From DESTINY‑Breast05
The sBLA is supported by results from the phase III DESTINY‑Breast05 trial, previously presented at the 2025 ESMO Congress and published in The New England Journal of Medicine. The study compared Enhertu with trastuzumab emtansine (T‑DM1) in 1,635 patients at high risk of recurrence following neoadjuvant therapy.
Major outcomes include:
- 53% reduction in the risk of invasive disease recurrence or death vs. T‑DM1
(HR 0.47; 95% CI 0.34–0.66; p<0.0001) - Three‑year invasive disease‑free survival:
- Enhertu: 92.4%
- T‑DM1: 83.7%
- 53% reduction in disease‑free survival events
- 51% reduction in distant recurrence risk
- 36% reduction in brain metastasis risk
- Safety profile consistent with prior studies, with no new concerns identified
AstraZeneca and Daiichi Sankyo leaders noted that these results highlight Enhertu’s potential to become a new standard of care for patients who remain at high risk even after initial HER2‑targeted treatment.
Regulatory Landscape and Broader Development
Regulatory reviews based on DESTINY‑Breast05 are also underway in the EU and Japan. Enhertu is simultaneously being evaluated in the US for use before surgery, in combination with paclitaxel, trastuzumab, and pertuzumab, supported by results from the DESTINY‑Breast11 trial.
Enhertu already holds approvals in more than 90 countries for various HER2‑positive, HER2‑low, and HER2‑ultralow metastatic breast cancer indications, as well as approvals in several other HER2‑driven solid tumor types and gastric cancer.
About Enhertu
Enhertu is an antibody–drug conjugate (ADC) that links a HER2‑targeted monoclonal antibody to a topoisomerase I inhibitor payload using a cleavable linker. It is jointly developed and commercialized by AstraZeneca and Daiichi Sankyo, with Daiichi Sankyo responsible for manufacturing.
Broader Context
Breast cancer remains one of the most common and deadly cancers worldwide, with more than two million diagnoses and over 665,000 deaths in 2022 alone. In the US, approximately 16,000 patients with HER2‑positive early breast cancer undergo treatment in the post‑neoadjuvant setting each year. Enhertu’s advancement in this space represents a significant step toward improving long‑term outcomes for these high‑risk patients.
