The Scottish Medicines Consortium has declined to recommend the Alzheimer’s therapy donanemab (Kisunla, Eli Lilly) for early-stage disease in NHS Scotland.
The decision affects patients with mild cognitive impairment and mild dementia caused by Alzheimer’s disease who are apolipoprotein E epsilon 4 heterozygotes or non-carriers, a genetic marker.
The consortium cited uncertainty over clinical relevance and economic viability despite clinical trial data showing statistically significant cognitive benefits over placebo for donanemab.
As a result, no disease-modifying treatment is currently available for Alzheimer’s disease within NHS Scotland, despite growing interest in amyloid-targeting treatments.
Clinical management will therefore continue to focus on symptomatic therapies, non-pharmacological interventions and supportive care.
Henry Simmons, chief executive of Alzheimer Scotland, described the ruling as “devastating for people living with dementia, their families and carers.”
He said it exposed fundamental flaws in how dementia drugs are assessed.
He called for dedicated pilot sites to test promising treatments in real-world settings before final NHS funding decisions are made, and urged the creation of a dementia drug innovation fund.
“We owe it to people who have waited decades for effective treatments to give these drugs a genuine chance to show their life-changing potential,” Simmons added.
Alzheimer’s disease affects more than 90,000 people in Scotland and is the most common form of dementia, accounting for around 66 per cent of cases.
The condition progresses from preclinical disease to severe dementia, with existing treatments limited to symptom management rather than disease modification.
Donanemab is a recombinant humanised immunoglobulin G1 monoclonal antibody, a type of targeted drug, that selectively binds to a modified form of amyloid-beta found in brain amyloid plaques, protein build-ups that are a pathological hallmark of the disease.
By targeting these plaques, the drug promotes their clearance through phagocytosis, a process where immune cells remove debris.
The recommended regimen consists of intravenous infusions every four weeks, starting with 700 milligrams for the first three doses, followed by 1,400 milligrams thereafter. Therapy should be discontinued if patients progress to moderate Alzheimer’s disease before completing treatment.
Treatment continues until amyloid plaque clearance is confirmed, or for a maximum of 18 months.
The phase three TRAILBLAZER-ALZ 2 study showed that donanemab slowed cognitive and functional deterioration at 76 weeks compared with placebo.
The trial enrolled 1,736 patients with gradual and progressive memory changes, amyloid pathology confirmed by PET imaging and specific tau pathology markers.
The primary endpoint measured changes in integrated Alzheimer’s Disease Rating Scale scores, which measure both cognition and daily function.
However, consortium clinical experts noted that this scale and the Clinical Dementia Rating Scale-Sum of Boxes are not routinely used in UK clinical practice, and views differed on whether changes exceeding 20 per cent on these scales represent clinically meaningful improvement for patients and families.
Amyloid-related imaging abnormalities were identified as the main safety concern.
ARIA-E, which refers to oedema or effusions, occurred in 24 per cent of patients receiving donanemab compared with 1.9 per cent of those receiving placebo, whilst ARIA-H, microhaemorrhages, occurred in 20 per cent versus 7.4 per cent respectively.
Most radiographic events developed within 24 weeks of treatment initiation, although they can occur at any time.
This necessitates brain MRI scans before treatment and during use, in line with the summary of product characteristics.
The committee expressed significant uncertainty about the “modest” clinical benefits observed in trials and how these would translate into real-world practice.
Implementation would also require substantial changes to services, including PET scans or cerebrospinal fluid analysis to verify beta-amyloid pathology, genetic testing for apolipoprotein E epsilon 4 status and regular MRI monitoring.
Clinical experts consulted by the consortium emphasised that these requirements would have major service implications and require considerable additional clinical capacity.
The rejection was driven largely by insufficient cost-effectiveness data.
Although the manufacturer estimated 422 eligible patients in the first year, rising to more than 2,100 by year five, the committee concluded that the long-term economic impact was disproportionate to the benefits offered.
This decision aligns with similar recent rulings by the National Institute for Health and Care Excellence in England and Wales.
Donanemab has, however, received regulatory approval for private use from the Medicines and Healthcare products Regulatory Agency.