ENHERTU Approval Reshapes Breast Cancer Care and Market

WILMINGTON, Del. – December 15, 2025 – The landscape of breast cancer treatment has been dramatically altered with the U.S. Food and Drug Administration's (FDA) approval of a new combination therapy from AstraZeneca and Daiichi Sankyo. ENHERTU®, when paired with pertuzumab, has been sanctioned as a first-line treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, marking the first such advancement in over a decade. This strategic milestone not only establishes a new benchmark for patient care but also cements the powerhouse status of the collaboration behind this innovative drug.

The approval, which followed a gauntlet of the FDA's most accelerated pathways—including Priority Review, Breakthrough Therapy Designation, and Real-Time Oncology Review—signals the agency's recognition of the therapy's profound potential to address a critical unmet need in a particularly aggressive form of cancer.

A New Benchmark in Clinical Efficacy

For years, the standard of care for patients newly diagnosed with HER2-positive metastatic breast cancer has been a combination of a taxane chemotherapy with two HER2-targeted antibodies, trastuzumab and pertuzumab (THP). While effective, most patients eventually see their disease progress, typically within about two years. The results from the pivotal DESTINY-Breast09 Phase III trial, however, have shattered that ceiling.

The data, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that the ENHERTU and pertuzumab combination reduced the risk of disease progression or death by a remarkable 44% compared to the long-standing THP regimen. Patients receiving the new combination experienced a median progression-free survival (PFS)—the length of time they live without their cancer worsening—of 40.7 months. This is a staggering 14-month improvement over the 26.9 months seen with the previous standard of care.

"Trastuzumab deruxtecan plus pertuzumab is the only 1st-line treatment approved in more than a decade to demonstrate a statistically significant improvement in progression-free survival," said Dr. Sara Tolaney, the trial's principal investigator from the Dana-Farber Cancer Institute. She asserted that with a median PFS exceeding three years, the combination "should become a new 1st-line standard of care in this setting." This sentiment has been echoed by oncologists who view the results as unequivocally practice-changing, offering patients extended periods of stability and a higher quality of life.

The Business of a Blockbuster Partnership

This clinical triumph is mirrored by a significant business victory for the Anglo-Swedish firm AstraZeneca and its Japanese partner, Daiichi Sankyo. Their 2019 collaboration to develop and commercialize ENHERTU has proven to be one of the most successful in recent pharmaceutical history. Following this latest US approval, AstraZeneca will make a $150 million milestone payment to Daiichi Sankyo, a fraction of the potential $5.5 billion in milestone payments outlined in their original agreement.

ENHERTU, a highly engineered antibody-drug conjugate (ADC), has become a cornerstone of both companies' oncology portfolios. Its market potential extends far beyond this new indication. Previous approvals for HER2-low and even HER2-ultralow breast cancer have already expanded its reach to a much larger patient population that previously had no HER2-targeted options. This has turned ENHERTU into a commercial juggernaut, with combined global sales reaching $3.754 billion in fiscal year 2024. Analysts project peak annual sales could surpass $5 billion, a forecast bolstered by this entry into the lucrative first-line metastatic setting, which sees approximately 10,000 new patients in the U.S. each year.

The market's reaction has been overwhelmingly positive, with the continued success of ENHERTU contributing to an 18% surge in Daiichi Sankyo's stock and a 12% gain for AstraZeneca in 2025. The drug is not just displacing older therapies like Kadcyla, another ADC it has outperformed in head-to-head trials, but is fundamentally reshaping the financial outlook for both partners, solidifying their leadership in the highly competitive and fast-growing ADC space.

Navigating Access, Cost, and Real-World Care

While the clinical benefits are undeniable, the introduction of this new standard of care brings practical challenges. The cost of ENHERTU is substantial, with a single vial priced at over $2,400 and estimated annual treatment costs potentially exceeding $165,000 per patient before insurance. When combined with the cost of pertuzumab, the regimen represents a significant financial consideration for patients, insurers, and healthcare systems.

To mitigate this, both companies have established patient assistance programs. Eligible commercially insured patients can utilize savings programs to reduce their out-of-pocket costs to as little as $0, with annual caps. However, access for patients on government plans remains a more complex issue. The high price tag will inevitably add pressure to healthcare budgets, forcing payers to weigh the therapy's profound clinical value against its cost.

Furthermore, clinicians must navigate the drug's safety profile. ENHERTU carries a boxed warning for interstitial lung disease (ILD), a serious and potentially fatal respiratory side effect. In the DESTINY-Breast09 trial, ILD occurred in 12% of patients, with 0.5% of cases being fatal. Other significant side effects include severe neutropenia (low white blood cell counts). Effective real-world implementation will depend on rigorous patient monitoring, education on reporting symptoms promptly, and proactive management by healthcare teams to balance the therapy's life-extending benefits with its risks.

A Global Rollout on the Fast Track

The rapid US approval was facilitated not only by compelling data but also by a strategic regulatory approach. The use of the FDA's Real-Time Oncology Review (RTOR) program allowed for a more collaborative and efficient review process, ensuring the therapy could reach patients as quickly as possible.

This domestic success is being leveraged for a swift global expansion. The submission was concurrently reviewed under Project Orbis, an FDA initiative that coordinates with international regulatory agencies. As a result, health authorities in Switzerland and Singapore are already reviewing the therapy, with decisions potentially coming much faster than through traditional pathways. This coordinated global strategy demonstrates the companies' ambition to make this new standard of care available to patients worldwide, further amplifying its impact on both public health and their bottom lines.