AstraZeneca and Daiichi Sankyo’s HER2-Targeted ADC Enhertu Granted Conditional Approval in the EU for Heavily Pretreated HER2-Positive Metastatic Breast Cancer

January 20, 2021 News /BioValleyBIOON/ ---AstraZeneca(AstraZeneca) and Daiichi Sankyo recently jointly announced that the European Commission (EC) has granted conditional approval to the HER2-targeted antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan): as a monotherapy for the treatment of unresectable or metastatic HER2-positiveBreast CancerAdult Patients.

Enhertu is jointly developed and commercialized globally by AstraZeneca and Daiichi Sankyo, with Daiichi Sankyo retaining exclusive rights in the Japanese market and taking full responsibility for manufacturing and supply.

In Europe, approximately 531,000 women are diagnosed with breast cancer each year, about 20% of whom are HER2-positive. The impact of this disease is substantial, with more than 141,000 deaths from breast cancer occurring annually.

This approval is based on a single-arm Phase IIClinical TrialData from DESTINY-Breast01:With a median follow-up of 20.5 months, Enhertu demonstrated a confirmed objective response rate (ORR) of 61.4%, including a complete response (CR) rate of 6.5% and a partial response (PR) rate of 54.9%; the estimated median duration of response (DOR) was 20.8 months.

Approximately 20% of breast cancer cases are HER2-positive. Despite therapeutic advances in recent years and the approval of multiple novel agents, there remains a significant unmet clinical need among patients with HER2-positive metastatic breast cancer. This disease remains incurable, and patients ultimately experience disease progression after receiving currently available therapies. HER2 is a growth-promoting tyrosine kinase receptor protein expressed in variousTumorCell surface, including gastric cancer, breast cancer, and lung cancer, is associated with aggressive disease and poor prognosis.

Enhertu is a next-generation antibody-drug conjugate (ADC) that links trastuzumab, a humanized monoclonal antibody targeting HER2, to a novel topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd) via a tetrapeptide linker. This enables targeted delivery of the cytotoxic agent into cancer cells, thereby reducing systemic exposure to the cytotoxic agent compared with conventional chemotherapy.

In March 2019, AstraZeneca and Daiichi Sankyo reached an agreement worth a total of $6.9 billion for immuneTumoracademic collaboration to jointly develop Enhertu for the treatment of patients with various cancers exhibiting different levels of HER2 expression or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and HER2-low breast cancer.

In the United States and Japan, Enhertu has been approved for the treatment of two types of cancer: (1) adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least two HER2-directed regimens; (2) patients with HER2-positive unresectable advanced or recurrent gastric cancer.

Approximately one-fifth of gastric cancer cases are HER2-positive. For patients with metastatic gastric cancer whose disease progresses after initial treatment with one anti-HER2 agent, there are no other approved HER2-targeted therapies available. Enhertu is the first antibody-drug conjugate (ADC) approved for the treatment of HER2-positive gastric cancer and the first and only HER2-targeted therapy demonstrated to significantly prolong overall survival (OS) compared with chemotherapy in patients with HER2-positive metastatic gastric cancer who had previously received chemotherapy and anti-HER2 therapy. According toClinical TrialsWith its compelling and robust efficacy, Enhertu will become the new standard of care in the clinical treatment of this patient population, bringing meaningful therapeutic advances to HER2-positive lung cancer.

The industry holds very optimistic views on the commercial prospects of Enhertu. Previously, the pharmaceutical market research firm EvaluatePharma predicted that Enhertu’s sales in 2024 would reach $2.5 billion. Other industry analysts have forecast that Enhertu’s annual peak sales will exceed $4 billion. (Bioon.com)

Original Source: Enhertuapproved in the EU for the treatment of HER2-positive metastatic breast cancer