AstraZeneca-Daiichi Sankyo Enhertu gets two breakthrough therapy designations in US for multiple HER2 expressing cancers

Tokyo: Daiichi Sankyo has announced that ENHERTU (fam-trastuzumab deruxtecan-nxki) has been granted two additional Breakthrough Therapy Designations (BTDs) in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, and for the treatment of patients with HER2 positive (IHC 3+) metastatic colorectal cancer who have received two or more prior regimens.

ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

HER2 overexpression has been observed in 1% to 28% across various types of metastatic solid tumors and in up to 5% of patients with colorectal cancer. There is an unmet need for effective therapies for these tumor types, particularly for patients who have progressed on or are refractory to standard of care therapies.

The U.S. Food and Drug Administration (FDA) 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.

The FDA granted the BTD for the treatment of metastatic HER2 positive solid tumors based on results from the ongoing DESTINY-PanTumor02 phase 2 trial with supporting data from other trials in the ENHERTU clinical development program. Results from an interim analysis of DESTINY-PanTumor02 were presented as a late-breaking oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in previously treated patients with HER2 expressing metastatic solid tumors including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancers and other tumors. The BTD for the treatment of HER2 positive metastatic colorectal cancer was based on final results from the DESTINY-CRC01 phase 2 trial presented at the 2022 ASCO Gastrointestinal Cancers Symposium (ASCO GI) and primary results from the DESTINY-CRC02 phase 2 trial presented at the 2023 ASCO Annual Meeting.

“ENHERTU is the first HER2 directed therapy to demonstrate a potential benefit across a series of difficult to-treat cancers and these designations are recognition of the continued potential of this innovative medicine,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We remain committed to exploring additional opportunities for ENHERTU in these tumor types with the goal of bringing this treatment to more patients as soon as possible.”

“This is an important step in bringing ENHERTU to patients with a broad range of HER2 expressing solid tumors who currently face a poor prognosis,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “We are encouraged by the recently reported results from our pantumor and colorectal cancer trials that contributed to these designations, and we look forward to working closely with the FDA to provide these patients with a potential new targeted treatment option.”

ENHERTU has received seven BTDs and its designation in HER2 expressing metastatic solid tumors represents the first time ENHERTU has been granted this designation in a tumor agnostic setting. ENHERTU previously received BTDs for three indications in breast cancer, including HER2 low metastatic breast cancer, second-line HER2 positive metastatic breast cancer and later-line HER2 positive metastatic breast cancer. Two additional BTDs for ENHERTU were granted for HER2 (ERBB2) mutant metastatic nonsmall cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer.

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