ENHERTU's EU Regulatory Breakthrough: A New Era for HER2-Targeted Oncology

AstraZeneca's ENHERTU (trastuzumab deruxtecan) has secured a pivotal regulatory milestone in the European Union, marking a transformative moment for the treatment of HER2-positive metastatic breast cancer. According to a report by AstraZeneca, the drug was approved in 2025 for adult patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer who have received at least one endocrine therapy in the metastatic settingEnhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-eu-in-post-et-breast-cancer.html]^[1]. This approval, based on the landmark DESTINY-Breast06 Phase III trial, positions ENHERTU as a groundbreaking therapy in a historically underserved patient populationEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2].

Regulatory Momentum and Clinical Evidence

The European Commission's decision followed a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) in late 2024Enhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2]. The trial demonstrated ENHERTU's superiority over chemotherapy, with a median progression-free survival (PFS) of 13.2 months compared to 8.1 months for chemotherapyEnhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-eu-in-post-et-breast-cancer.html]^[1]. Notably, the drug reduced the risk of disease progression or death by 38% in the overall trial population, which included patients with HER2-low and HER2-ultralow tumorsEnhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-eu-in-post-et-breast-cancer.html]^[1]. These results underscore ENHERTU's ability to address a critical unmet need in oncology, where traditional HER2-targeted therapies have shown limited efficacy for low-expression tumorsEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2].

Market Differentiation and Competitive Edge

ENHERTU's approval in the EU cements its status as the first HER2-directed therapy for HR-positive, HER2-low or ultralow metastatic breast cancer. Unlike conventional HER2-targeted agents such as trastuzumab or pertuzumab, which require high HER2 expression levels to be effective, ENHERTU leverages its antibody-drug conjugate (ADC) technology to deliver a cytotoxic payload to both high- and low-expression tumorsEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2]. This broadens its therapeutic applicability and differentiates it from competitors in the HER2-positive oncology space.

The drug's mechanism also offers a favorable safety profile compared to chemotherapy, which is often associated with severe side effects. While interstitial lung disease remains a concern, ENHERTU's tolerability is generally better than traditional cytotoxic regimens, enhancing its appeal for long-term use in metastatic settingsEnhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-eu-in-post-et-breast-cancer.html]^[1].

Long-Term Commercial Potential

The EU approval opens a significant commercial opportunity for ENHERTU. HR-positive, HER2-low or ultralow metastatic breast cancer represents a large and growing patient population, with estimates suggesting that up to 50% of metastatic breast cancer cases fall into this categoryEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2]. By securing early adoption in this niche, AstraZeneca can establish ENHERTU as a first-line treatment, driving revenue growth in a market projected to expand with increased HER2 testing and ADC adoption.

Moreover, the approval aligns with a broader industry shift toward precision oncology. As diagnostic capabilities improve, the ability to stratify patients based on HER2 expression levels will become standard practice, further amplifying ENHERTU's market reachEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2]. Analysts estimate that the EU market for HER2-targeted ADCs could exceed €2 billion annually by 2030, with ENHERTU poised to capture a dominant share due to its clinical differentiationEnhertu approved in the EU as first HER2-directed therapy for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-eu-in-post-et-breast-cancer.html]^[1].

Challenges and Strategic Considerations

Despite its promise, ENHERTU faces challenges. Competition from other ADCs, such as Roche's sacituzumab govitecan, and potential pricing pressures in cost-conscious EU markets could temper growth. Additionally, the need for robust companion diagnostics to identify HER2-low/ultralow patients may slow adoption in regions with limited access to advanced testingEnhertu recommended for approval in the EU by CHMP ..., [https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-recommended-approval-eu-chmp-patients-low-ultralow-metastatic-breast-cancer-following-least-one-endocrine-therapy.html]^[2].

However, AstraZeneca's strong commercial infrastructure and ongoing trials in earlier-stage breast cancer and other HER2-expressing tumors (e.g., gastric cancer) provide a buffer against these risks. Expanding ENHERTU's label to additional indications could further solidify its long-term value.

Conclusion

ENHERTU's EU approval represents a strategic win for AstraZeneca, combining regulatory validation, clinical differentiation, and a clear path to market leadership. For investors, the drug exemplifies the transformative potential of ADC technology in oncology. As precision medicine reshapes cancer care, ENHERTU's ability to deliver targeted, durable responses in a high-prevalence patient population positions it as a cornerstone of future oncology portfolios.