AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) has been accepted and granted Priority Review by the US Food and Drug Administration (FDA) for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who have undergone prior treatment or have no satisfactory alternative treatment options.
The sBLA submission is grounded in compelling data from the ongoing DESTINY-PanTumor02 Phase II trial. Enhertu exhibited clinically meaningful and durable responses, leading to a significant survival benefit in previously treated patients across HER2-expressing metastatic solid tumors. These include biliary tract, bladder, cervical, endometrial, ovarian cancers, and other tumors. Supporting trial data from other studies within the Enhertu clinical development program, such as DESTINY-Lung01 and DESTINY-CRC02, were also included in the submission.
Enhertu, a HER2-directed antibody drug conjugate (ADC) engineered specifically, is a collaborative effort between AstraZeneca and Daiichi Sankyo.
The FDA granted Priority Review based on the potential of Enhertu to provide substantial improvements over existing options by demonstrating efficacy improvements or safety, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, representing the FDA action date for their regulatory decision, is anticipated in the second quarter of 2024.
Susan Galbraith, Executive Vice President, Oncology R&D at AstraZeneca, expressed, “Today’s Priority Review for the first tumour-agnostic submission for Enhertu reflects the potential of this medicine to redefine the treatment of HER2-expressing cancers.” She emphasized the importance of identifying HER2 expression across various tumor types.
Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, highlighted the clinical benefits seen in the DESTINY-PanTumor02 trial and ongoing data from the Enhertu clinical development program, stating, “If approved, Enhertu could become the first HER2-directed therapy and antibody drug conjugate with a tumor-agnostic indication, providing patients with a potential new treatment option.”
The sBLA is undergoing review through the Real-Time Oncology Review (RTOR) program and Project Orbis, initiatives designed by the FDA to expedite the availability of safe and effective cancer treatments. RTOR allows the FDA to assess components of an application before the complete submission, while Project Orbis facilitates concurrent submission and review of oncology medicines among participating international partners.
Results from DESTINY-PanTumor02 were presented at the 2023 European Society for Medical Oncology Congress and published in the Journal of Clinical Oncology. The safety profile observed across trials remained consistent with previous clinical trials of Enhertu, with no new safety concerns identified. The Priority Review comes after the receipt of Breakthrough Therapy Designation (BTD) in August 2023 for Enhertu in metastatic HER2-positive solid tumors.
