ENHERTU® Granted Priority Review in the U.S. as Post-Neoadjuvant Treatment for Patients with HER2 Positive Early Breast Cancer

Key Takeaways

• ENHERTU reduces recurrence risk 53% vs T‑DM1
• Three‑year IDFS reaches 92.4% with ENHERTU
• Distant recurrence risk lowered 51% with ENHERTU
• Interstitial lung disease observed in 9.6% of ENHERTU patients
• FDA priority review targets decision by July 7, 2026

Summary

Daiichi Sankyo and AstraZeneca have received FDA priority review for ENHERTU® as a post‑neoadjuvant therapy in HER2‑positive early breast cancer. The decision follows the DESTINY‑Breast05 phase 3 trial, which showed a 53% reduction in invasive disease‑free survival events versus trastuzumab‑emtansine (T‑DM1). Three‑year IDFS reached 92.4% with ENHERTU compared with 83.7% for T‑DM1, and distant recurrence risk fell 51%. The agency’s PDUFA target date is July 7, 2026.

Pulse Analysis

HER2‑positive early breast cancer remains a therapeutic challenge, especially for the roughly half of patients who retain residual invasive disease after neoadjuvant HER2‑targeted therapy. Post‑neoadjuvant treatment is critical to prevent progression to metastatic disease, and antibody‑drug conjugates (ADCs) have emerged as a powerful strategy. ENHERTU, a trastuzumab‑deruxtecan ADC built on Daiichi Sankyo’s DXd platform, delivers a potent cytotoxic payload directly to HER2‑expressing cells, aiming to eradicate microscopic residual tumors while sparing normal tissue.

The DESTINY‑Breast05 phase 3 trial enrolled 1,635 patients and demonstrated that ENHERTU markedly outperformed T‑DM1. The hazard ratio for invasive disease‑free survival was 0.47, translating to a 53% relative risk reduction, and three‑year IDFS reached 92.4% versus 83.7% for the comparator. Secondary endpoints also favored ENHERTU, with a 51% drop in distant recurrence and a 36% reduction in brain metastasis risk. Safety was comparable; grade 3+ adverse events occurred in 50.6% of ENHERTU patients versus 51.9% with T‑DM1, though interstitial lung disease was observed in 9.6% of the ENHERTU arm, underscoring the need for vigilant monitoring.

The FDA’s priority review, following a Breakthrough Therapy designation, reflects the agency’s confidence that ENHERTU could deliver a meaningful clinical advantage. Reviewed under the Project Orbis framework, the decision is slated for July 7, 2026, with parallel submissions ongoing in the EU and Japan. Approval would not only shift the post‑neoadjuvant landscape away from T‑DM1 but also reinforce the growing role of ADCs in early‑stage oncology, potentially expanding market share for both Daiichi Sankyo and AstraZeneca while prompting competitors to accelerate their own HER2‑targeted pipelines.