6 October 2021 - - The US Food and Drug Administration has granted Enhertu (fam-trastuzumab deruxtecan-nxki) Breakthrough Therapy Designation in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens, British-Swedish pharmaceutical and biotechnology company AstraZeneca (NASDAQ: AZN) said.

Enhertu is a HER2-directed antibody drug conjugate jointly developed by AstraZeneca and Japan-based Daiichi Sankyo Company, Ltd.

The FDA granted BTD based on data from the DESTINY-Breast03 registrational trial presented during the European Society for Medical Oncology Congress 2021.

This is the second BTD for Enhertu in breast cancer and now brings the total number of BTDs to four for this medicine.

The US FDA's BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need.

The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

Breast cancer remains the most common cancer worldwide, with more than two m cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.

Approximately one in five cases of breast cancer are considered HER2-positive.2 Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.

More effective options are needed to further delay progression and extend survival.

In DESTINY-Breast03, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p=7.8x10-22) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

Nearly all patients treated with Enhertu were alive at one year (94.1%) compared to 85.9% of patients treated with T-DM1.

Confirmed objective response rate more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%).

The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

Previous BTDs for Enhertu were in late-line HER2-positive metastatic breast cancer in 2017 and HER2-mutant metastatic non-small cell lung cancer (NSCLC) and HER2-positive metastatic gastric cancer in 2020.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting in the US, Japan, the EU and several other countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development program evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with Enhertu 5.4 mg/kg, ILD occurred in 9% of patients.

Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with Enhertu. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with Enhertu 6.4 mg/kg, ILD occurred in 10% of patients.

Median time to first onset was 2.8 months (range: 1.2 to 21.0).

British-Swedish pharmaceutical and biotechnology company AstraZeneca (NASDAQ: AZN) has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment.