The National Institute for Health and Care Excellence (NICE) has issued draft guidance rejecting the use of lecanemab (Leqembi; Eisai) and donanemab (Kisunla; Eli Lilly) for treating Alzheimer's disease (AD) within the National Health Service (NHS) in England and Wales. Despite both monoclonal antibody treatments receiving approval from the Medicines and Healthcare products Regulatory Agency (MHRA) for use in the UK, NICE concluded that their cost-effectiveness has not been sufficiently demonstrated to warrant widespread NHS adoption. This decision arrives despite the drugs' ability to target the root cause of the disease and slow its progression, marking a significant point of contention within the AD treatment landscape.
NICE's Concerns Over Cost and Side Effects
NICE acknowledged that both lecanemab and donanemab can slow the progression of AD; however, the organization stated that more evidence was needed to generate robust cost-effectiveness estimates. For lecanemab, NICE noted that while the drug slows AD progression by four to six months, the cost of delivering the drug and monitoring for side effects, combined with the relatively small benefits, meant that it was not considered a cost-effective use of limited NHS funding. Similarly, for donanemab, NICE acknowledged that it can slow AD progression by four to seven months, but said that there were uncertainties around the economic modelling. It concluded that the cost-effectiveness estimate is likely to be above what NICE normally considers an acceptable use of NHS resources.
The costs associated with administering these treatments, including fortnightly infusions and intensive monitoring for amyloid-related imaging abnormalities (ARIAs), such as brain swelling or bleeding, were key factors in NICE's assessment. Clinical trial data for donanemab showed ARIA-E (brain oedema or sulcal effusion) occurred in 24.0% of participants in the donanemab group compared to 2.1% in the placebo group. For lecanemab, the rate of radiographically identified ARIA-E was 12.6% for lecanemab and 1.7% for placebo.
Implications for Patient Access and Future Research
The MHRA's approval contrasted with NICE's rejection means that lecanemab and donanemab will likely only be accessible to patients who can afford private healthcare. Lecanemab costs approximately £20,000 per year in the United States, with total care costs potentially reaching hundreds of thousands of pounds due to the need for intravenous administration every other week, extensive screening tests, and ongoing MRI scans to monitor side effects.
Experts have expressed mixed reactions to NICE's decision. Some, like Hilary Evans-Newton, chief executive of Alzheimer's Research UK (ARUK), described the lecanemab decision as deeply disappointing, while others, such as Robert Howard, professor of Old Age Psychiatry at University College London, said the decision should not come as a surprise. Tara Spires-Jones, group leader at the UK Dementia Research Institute at the University of Edinburgh, emphasized the need to double down on research efforts to find new, affordable diagnostic tools and different treatment options that can be implemented more easily in our health system.
Global Availability and Future Decisions
Lecanemab has been approved in the United States, Japan, China, South Korea, Hong Kong, and Israel, and is being marketed in the United States, Japan, and China. Donanemab has been approved in both the United States and Japan. However, the European Medicines Agency (EMA) refused marketing authorization approval for lecanemab in July 2024, citing that the observed effect of the treatment on delaying cognitive decline does not counterbalance the risk of serious adverse events associated with the medicine. A final decision on lecanemab is due in February 2025, and a final decision on donanemab is due in March 2025.
Current Treatments and Future Therapies
Current treatments for AD in the UK focus on managing symptoms and include acetylcholinesterase (AChE) inhibitors and memantine. Several new therapies are in the pipeline, including remternetug, buntanetap, and semaglutide, offering potential future treatment options for AD.
