USFDA grants priority review to AstraZeneca-Daiichi Sankyo Enhertu for HER2-low, HER2 Ultralow Breast Cancer

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025.

Enhertu was also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. Despite being classified as HER2-negative, many of these tumours still carry some level of HER2 expression. It is estimated that up to 85-90% of tumours historically classified as HR-positive, HER2-negative, may be HER2-low or HER2-ultralow.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is associated with poor response rates and outcomes. The results from DESTINY-Breast06 show that Enhertu has the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said, “This Priority Review highlights the potential to expand the existing indication of Enhertu in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow. We look forward to working closely with the FDA with the goal of bringing Enhertu to more patients as quickly as possible.”

The sBLA is based on data from the DESTINY-Breast06 Phase III trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and recently published in The New England Journal of Medicine.

In the trial, Enhertu reduced the risk of disease progression or death by 37% by blinded independent central review (BICR) versus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.53-0.75; p<0.0001) in the overall trial population. Median PFS was 13.2 months with Enhertu compared to 8.1 months with chemotherapy.

Results were consistent between patients with HER2-low expression and HER2-ultralow expression. In the primary endpoint analysis of patients with HER2-low expression, Enhertu showed a median PFS of 13.2 months compared to 8.1 months for chemotherapy (HR 0.62; 95% CI 0.51-0.74; p<0.0001). In a prespecified exploratory analysis of patients with HER2-ultralow expression, Enhertu showed a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI 0.50-1.21).

The safety profile of Enhertu in DESTINY-Breast06 was consistent with previous clinical trials of Enhertu in breast cancer with no new safety concerns identified.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu is already approved in more than 65 countries, including the US, for patients with HER2-low metastatic breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.