A “number of issues” likely to arise during NICE’s evaluation of new dementia treatments

The National Institute for Health and Care Excellence (NICE) has published a new report outlining the potential issues and challenges in evaluating disease-modifying dementia treatments (DMDTs).

The report has outlined various obstacles, including the uncertain disease prevalence estimates and the need for invasive diagnostics for identifying the treatment eligible population.

While there are currently no licensed DMDTs in the UK, several are at varying stages of development and regulatory approval, such as lecanemab and donanemab.

These treatments are scheduled to be appraised by NICE next year, but the report aims to address any concerns head ahead of the appraisal process.

1.5 million people expected to be living with dementia by 2040

Research from 2019 estimates there were over 850,000 people with dementia in the UK, representing one in every 14 people aged 65 years and over.

If this trajectory continues, it is estimated that will be roughly 1.5 million people living with dementia in the UK by 2040.

Alzheimer’s disease, the most common type of dementia, is characterised by the abnormal build-up of proteins called amyloid beta in and around brain cells. This process is thought to cause cognitive and functional decline and behavioural non-cognitive symptoms.

While there are currently no licensed treatments which target the underlying cause of the disease, emerging DMDTs aim to cause an enduring change in the clinical progression of Alzheimer’s disease by targeting this protein build up in the brain.

Since these treatments are the first to target the pathophysiological mechanisms of the disease process, NICE determined there were likely to be some key issues that would arise during their evaluations.

Challenges identifying those with mild cognitive impairment

One of these issues is the uncertainty over how many people may have mild cognitive impairment. This means thousands of people may need invasive tests to identify those who may be eligible for new treatments.

Since Alzheimer’s is so common, effecting one in every 14 people aged 65 years and over, NICE says introducing these tests at the necessary scale “represents a major change in the current management pathway.”

Currently, there is also no published data on the long-term treatment effectiveness of DMDTs, and NICE says data from the latest research trials will need to be extrapolated to infer their lifetime benefit.

NICE is also evaluating the cost effectiveness of these new treatments. Since both lecanemab and donanemab are administered intravenously in hospitals, a cost analysis will need to be conducted to consider these additional costs, as well as the associated injection site reactions and complications.

There is also concern about the incidence of adverse events and the need for regular monitoring. ARIA is a major adverse event seen in the trials of anti-amyloid beta DMDTs, and commentary from experts during an engagement workshop highlighted that more frequent MRI scans and other clinical assessments would be required in the real-world use of DMDTs.

As well as the extra resources needed, NICE says the impact of these adverse events on the health-related quality of life of people having these treatments and their carers should also be considered, and communication with patients and their families about the risks would be necessary.

NICE’s current evaluation approach “appropriate” for evaluating DMDTs

Therefore, NICE concludes that it is likely to encounter “a number of key issues” during its evaluation of DMDTs.

Despite these anticipated challenges, NICE says their current approach to evaluating these treatments is considered “appropriate.”