The Scottish Medicines Consortium (SMC) has declined to recommend donanemab  (Kisunla, Eli Lilly) for use in NHS Scotland for early-stage Alzheimer's disease , citing uncertainty over clinical relevance and economic viability. 

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, despite clinical trial data showing statistically significant cognitive benefits over placebo.

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-pharmacologic interventions, and supportive care.

Patient Groups React

Patient organisations acknowledged widespread disappointment over the decision, while stressing the need for treatments that deliver clear, meaningful benefits without compromising safety.

Henry Simmons, chief executive of Alzheimer Scotland, described the ruling  as “devastating for people living with dementia, their families and carers,” saying it exposed fundamental flaws in how dementia drugs are assessed.

He called for dedicated pilot sites to test promising therapies 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% of cases. The condition progresses from preclinical disease to severe dementia, with existing treatments limited to symptom management rather than disease modification.

How the Therapy Works

Donanemab is a recombinant humanised immunoglobulin G1 monoclonal antibody that selectively binds to a modified form of amyloid-beta found in brain amyloid plaques, a pathological hallmark of Alzheimer’s disease. By targeting these plaques, the drug promotes their clearance through phagocytosis.

The recommended regimen consists of intravenous infusions every 4 weeks, starting with 700 mg for the first three doses, followed by 1400 mg thereafter. Treatment continues until amyloid plaque clearance is confirmed, or for a maximum of 18 months. Therapy should be discontinued if patients progress to moderate Alzheimer’s disease before completing treatment.

Functional and Cognitive Outcomes

The phase 3 TRAILBLAZER-ALZ 2  study showed that donanemab slowed cognitive and functional deterioration at 76 weeks compared with placebo.

The trial enrolled 1736 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 (iADRS) scores, which measure both cognition and daily function. However, SMC clinical experts noted that iADRS 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% on these scales represent clinically meaningful improvement for patients and families.

Safety Concerns

Amyloid-related imaging abnormalities (ARIA) were identified as the main safety concern. ARIA-E (oedema or effusions) occurred in 24% of patients receiving donanemab compared with 1.9% of those receiving placebo, whilst ARIA-H (microhaemorrhages) occurred in 20% vs 7.4%, 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 therapy, in line with the summary of product characteristics.

Clinical and Economic Considerations

The SMC committee expressed significant uncertainty about the "modest" clinical benefits observed in trials and how these would translate into real-world practice. Experts noted that trial endpoints, such as the iADRS, are not typically used in routine care, complicating assessments of "meaningful" improvement.

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 SMC 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 2100 by year 5, 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.