ENHERTU and the changing economics of access to innovation in the NHS in England
The revised recommendation is significant beyond ENHERTU itself. It follows changes to NICE’s cost-effectiveness framework and comes amid a UK pharmaceutical pricing environment increasingly shaped by international considerations, including the UK–US pharmaceutical agreement. The decision therefore offers an early illustration of how greater economic flexibility may help innovative medicines reach NHS patients.
An innovative treatment in an area of substantial unmet need
HER2-low breast cancer is defined by low levels of HER2 protein expression: an immunohistochemistry (IHC) score of 1+, or 2+ with a negative in situ hybridisation result. It is distinct from HER2-positive disease, for which HER2-targeted treatments have long been established. Patients with unresectable or metastatic HER2-low breast cancer who have already received chemotherapy have historically had limited subsequent treatment options, making improvements in disease control and survival particularly valuable.
ENHERTU is an antibody–drug conjugate (ADC) developed by Daiichi Sankyo and AstraZeneca. It combines a HER2-targeting antibody with a potent topoisomerase I inhibitor, joined by a cleavable linker. The antibody directs the treatment towards cells expressing HER2, where the cytotoxic payload can be released. This approach has helped establish ENHERTU as one of the leading treatments amongst the emerging class of ADCs. [4]
The pivotal DESTINY-Breast04 trial demonstrated improvements using ENHERTU compared with the physician’s choice of chemotherapy. In the hormone-receptor-positive cohort, median overall survival was 23.9 months versus 17.5 months (p=0.003), while median progression-free survival was 10.1 months versus 5.4 months (p<0.0001). These findings provided a compelling clinical case for ENHERTU. Combined with its innovative technology and the substantial unmet need, they provided compelling reasons for reimbursement.
From clinical benefit to an economic impasse
Despite this clinical evidence, NICE decided in July 2024 not to recommend ENHERTU for routine NHS use in the relevant HER2-low population. The decision was not a rejection of the treatment’s clinical effectiveness. Rather, the committee considered the cost-effectiveness estimates too uncertain and, under its preferred assumptions, above the level it could accept.
A central issue was the economic model’s projection of overall survival beyond the observed trial data. Assumptions about patients’ quality of life after disease progression also affected the estimated quality-adjusted life years (QALYs) gained. These modelling choices are particularly important for a treatment that extends survival: differences in the projected duration and quality of that benefit can materially change the incremental cost-effectiveness ratio (ICER).
Commercial discussions did not produce terms that resolved the committee’s concerns. For patients who might have benefited from ENHERTU but could not access it routinely through the NHS, the decision was a devastating setback.
Patient organisations, including Breast Cancer Now, Make 2nds Count and MET UP UK, continued to press for a solution. Their advocacy kept attention on the consequences of delayed access for people living with advanced disease. The joint campaign amongst the three organisations included two petitions gathering more than 385,000 signatures and a high-profile public event in London’s Trafalgar Square. [5, 6, 7]
Meanwhile, in December 2025, NICE announced changes to its cost-effectiveness thresholds, moving the standard range to £25,000–£35,000 per QALY gained. This created a new context in which the economic case for ENHERTU could be reconsidered. These changes became official in April 2026. Following this, the patient associations campaigned for ENHERTU’s case to be revisited, which in June resulted in an Early Day Motion supported by 65 members of the UK parliament. This urged the NHS, AstraZeneca and Daiichi Sankyo to reach a deal and enable access. [8, 9]
What changed in 2026?
In July, NICE convened a rapid review of ENHERTU for HER2-low advanced breast cancer. This led to positive final draft guidance in September recommending routine use. Notably, the revised conclusion did not depend on a fundamentally new understanding of ENHERTU’s clinical efficacy. Instead, the assessment brought together three changes that improved the economic case. [2]
First, the revised cost-effectiveness thresholds expanded the range within which an innovative treatment could be considered cost effective. In the ENHERTU reassessment, NICE’s committee agreed that an ICER of around £35,000 per QALY gained would be acceptable, compared with around £30,000 in its 2024 assessment. This provided additional headroom for a positive recommendation.
Second, the revised economic analysis used the new UK EQ-5D-5L value set directly, rather than mapping EQ-5D-5L responses to the older three-level measure. This changed how health-related quality of life was valued in progression-free and post-progression states. Given the importance of utility assumptions in the original assessment, it was a consequential update to the economic case rather than a minor technical adjustment.
Third, the revised assessment incorporated updated confidential commercial terms. As these discounts remain confidential, we cannot say for sure to what extent this contributed to the revised affordability of the drug.
A wider negotiating window, not a resolution of affordability pressures
The ENHERTU decision offers a practical example of what NICE’s revised framework may achieve. A treatment whose clinical benefits were already recognised has received a positive recommendation following changes to the economic assessment and commercial terms. This is a very positive move for patients, giving them more time and hope.
It does not follow, however, that the NHS can accommodate substantially higher medicine prices across the board. NICE has estimated that the revised thresholds could support recommendations for approximately three to five additional medicines or indications each year. Against a baseline of around 70 positive recommendations annually, this represents an increase of approximately 4–7%. This represents an expansion of access, but a relatively limited one. [9]
Higher cost-effectiveness thresholds also have funding consequences. The Government has said that additional costs will initially be met from existing NHS budgets, alongside expenditure on current services and medicines. Future funding will be determined at the next Spending Review. Greater flexibility in appraisal decisions therefore does not, by itself, resolve the wider question of affordability.
The UK–US pharmaceutical agreement has also attracted scrutiny. MPs have sought further information about its economic impact assessment, while the Government has said that it does not plan to publish the assessment because it contains commercially sensitive information. So, for the time being at least, it appears that this issue will remain politically sensitive and subject to further debate in the coming months. [10]
For manufacturers, the implications are nuanced. Greater flexibility may make it easier to find commercially sustainable terms for some treatments, particularly where an economic case sits near the previous threshold. Yet it does not remove the need to demonstrate value convincingly, address material modelling uncertainty, plan for local market access or negotiate an acceptable net price.
Making innovation available sooner
It took approximately two years to move from NICE’s original decision to a positive recommendation for ENHERTU. During that period, some patients who might have been eligible for treatment will have died. This underlines the serious consequences that prolonged access processes can have for patients and their loved ones. The question now is whether the ENHERTU case points towards faster access to innovative treatments in the future.
My view is that the changes represent incremental reform rather than a fundamental redesign of the system. They respond to issues that patients and the life sciences sector have raised for many years. However, it’s my view that their effect on access is likely to remain modest and concentrated among technologies for which commercially acceptable terms are within reach. ENHERTU appears to have been one such case. Other treatments, with different cost structures or greater uncertainty in their economic evidence, may remain difficult to accommodate.
For developers of innovative medicines, the lesson is to explore the available economic levers thoroughly and identify where an agreement may be possible. In ENHERTU’s case, the revised recommendation reflected changes to the acceptable cost-effectiveness benchmark, the valuation of quality of life and the commercial arrangement. Where delays cannot be avoided, manufacturers should also consider whether other appropriate access channels are available.
For the wider system, the challenge is to build on these changes and find ways to reach workable decisions sooner, particularly when patients have limited alternatives and time matters.
Contact
If you are interested in discussing any of the issues above for your company/drug development program, please contact me through my email address dniven@nivenbiopharma.com. Feel free to also visit my website at www.nivenbiopharma.com for more information. I have no conflicts of interest in the production of this article.
Sources
[1] NICE recommends Enhertu for people with HER2-low advanced breast cancer, NICE, 17 September 2026
[2] Trastuzumab deruxtecan for treating HER2-low metastatic or unresectable breast cancer after chemotherapy (Final Draft Guidance), NICE, 17 September 2026
[3] Trastuzumab deruxtecan for treating HER2-low metastatic or unresectable breast cancer after chemotherapy, NICE, 29 July 2024
[4] ENHERTU: EPAR – Product Information, EMA, version dated 20 July 2026
[5] Breast Cancer Now respond to devastating NICE decision to not recommend life-extending breast cancer drug Enhertu for NHS use in England, Breast Cancer Now, 29 July 2024
[6] Open Letter to Wes Streeting MP on UK-wide access to Enhertu, Make 2nds Count, 21 Jan 2026
[7] Enhertu Now - We did it!, Breast Cancer Now website
[8] Enhertu for metastatic breast cancer patients, UK Parliament, 1 June 2026
[9] Changes to NICE’s cost-effectiveness thresholds confirmed, NICE, 1 December 2025
[10] MPs seek probe into UK-US pharma deal's impact on NHS, Pharmaforum, 18 September 2026
