NICE to Review Alzheimer's Drug Guidance After Appeals Upheld

The National Institute for Health and Care Excellence (NICE) has upheld appeals to review its final guidance to the NHS on the use of two new Alzheimer's medicines. The decision means the treatments will return to a NICE committee for further consideration after manufacturers argued that NICE had failed to properly account for the wider impact of the treatments, including the heavy burden on unpaid carers.

Eisai and Eli Lilly, the manufacturers of lecanemab and donanemab, appealed last year's decision by NICE that the medicines were too expensive to provide on the NHS in England and Wales. The manufacturers argued that NICE had failed to properly account for the wider impact of the treatments, including the heavy burden on unpaid carers.

Alzheimer's Research UK welcomed the ruling, stating it is "an opportunity for NICE to consider the real cost of Alzheimer's on people and their families." The organization noted that dementia places a huge and often hidden burden on families, with unpaid care costing the economy over £20bn a year. Research has delivered new treatments with the potential to provide people with valuable extra months of independence, lessening the burden on carers.

While these treatments offer modest benefits and can cause serious side effects, they provide the foundation for a future where dementia becomes a treatable condition. Growing evidence from the use of these medicines shows they can slow the progression of the disease.

The news comes amid broader challenges in neurodegenerative disease research. Recent failures in high-profile clinical trials of neurodegenerative diseases highlight the need to rebalance clinical ambition and biological understanding. Novo Nordisk recently announced that the oral GLP-1 receptor agonist drug semaglutide failed to slow disease progression in Alzheimer's disease in two highly anticipated phase 3 clinical trials. This news came within hours of Johnson & Johnson's announcement that it had stopped the phase 2 trial of their tau-targeting therapy posdinemab after a scheduled data review found no slowing of cognitive decline, compared with placebo.

These trial outcomes can easily be attributed to the inherent complexity of neurodegenerative diseases or dismissed as typical pipeline troubles. However, a more uncomfortable alternative is that it reflects a growing trend to test interventions on a clinical scale before fully understanding which mechanisms drive disease, when they matter and in whom they are relevant.

Neurodegenerative disease-associated pathways unfold in humans over decades, compensatory mechanisms are common and clinical symptoms often occur only at the late stage of disease. This, coupled with the inaccessibility of diseased tissues, often relegates mechanistic studies to preclinical models with limited human relevance. These constraints make it difficult to determine when there is sufficient mechanistic support for a target or agent to enter clinical trials.