The U.S. Food and Drug Administration (FDA) has approved the use of Enhertu, an antibody-drug conjugate developed by AstraZeneca and Daiichi Sankyo, as a first-line treatment for patients with metastatic, HER2-positive breast cancer. The approval allows Enhertu to be used in combination with Roche’s HER2 blocker Perjeta.
Analysts at Jefferies commented on the significance of this development: “First-line approval is highly significant because it expands the total addressable market to patients who typically remain on therapy much longer than those in later lines.” They noted that while some demand may shift from second-line use, earlier adoption could add $2 billion to $3 billion to Enhertu’s peak sales, bringing projections up to $10 billion to $12 billion.
The FDA’s decision was based on data from the DESTINY-Breast09 study. According to results presented at the American Society of Clinical Oncology meeting in June, the combination of Enhertu and Perjeta reduced the risk of disease progression or death by 44% compared to a regimen containing taxane, Herceptin, and Perjeta. The objective response rate in the Enhertu group was 85.1%, with 15.1% achieving complete responses. The median duration of response reached 39.2 months.
This latest approval adds to a series of regulatory successes for Enhertu this year. In January, it became the first HER2-targeting therapy approved by the FDA for patients with unresectable or metastatic breast cancer exhibiting ultralow levels of HER2 expression. In April, European regulators also approved its use for this population after at least one prior line of endocrine treatment.
Enhertu targets HER2 and delivers a topoisomerase I inhibitor payload directly to cancer cells, disrupting their genomes and leading to cell death. Initially approved in December 2019 for third-line treatment of HER2-positive breast cancer, Enhertu has since received additional approvals, including a tumor-agnostic indication for HER2-positive cancers in April 2024.
AstraZeneca and Daiichi Sankyo are exploring further uses for Enhertu beyond breast cancer. In March, they reported that the drug showed statistically significant improvement in overall survival among patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer. An external data monitoring board recommended stopping that study early due to “superior efficacy.” The companies have indicated plans to discuss these findings with regulators but have not announced when they will file for approval.
