AstraZeneca and Daiichi Sankyo have received notification of acceptance of the supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen. The application has also been granted Priority Review.
Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
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.1 The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the second quarter of 2022.
The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) programme and Project Orbis, two initiatives of the FDA which are designed to bring effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners.
Breast cancer is the most common cancer worldwide, with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.2 Approximately one in five cases of breast cancer are considered HER2-positive.3 Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4-6
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: "This review across geographies and the Priority Review in the US as part of Project Orbis is so important because it speaks to the transformative potential of Enhertu based on the unprecedented progression-free survival benefit in this setting. The news reinforces the importance of bringing this potential new option to patients as quickly as possible."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This regulatory review of Enhertu in the US marks the first time this medicine is participating in both the Real-Time Oncology Review and Project Orbis programmes. The FDA's prioritisation of our application underscores the potential of this medicine and the continued need to expedite the availability of new treatment options, while making it possible to potentially receive approvals in several countries concurrently."
The sBLA is based on data from the DESTINY-Breast03 trial presented during the European Society for Medical Oncology (ESMO) Congress 2021.
In the trial, 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.
DESTINY-Breast03 also recorded that nearly all patients treated with Enhertu during the trial were alive at one year (94.1%) compared to 85.9% of patients treated with T-DM1. Confirmed objective response rate (ORR) 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.
In September 2021, Enhertu received its fourth Breakthrough Therapy Designation (BTD) 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.
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 more than 30 countries based on the results from the DESTINY-Breast01 trial.
Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
Notes
HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.2 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.2 Approximately one in five cases of breast cancer are considered HER2-positive.3
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8
Despite initial treatment with trastuzumab and a taxane, people with HER2-positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4-6
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, ORR, duration of response, PFS based on investigator assessment and safety.
