A new drug in old systems: lecanemab will only be as effective as public health

By Cecilia Price

A new drug, lecanemab*, has been hailed as a ‘momentous breakthrough’ in Alzheimer’s disease research. Whilst so much of dementia care centers around management of symptoms and improving quality of life, lecanemab actually holds the potential to slow the progression of Alzheimer’s disease by attacking the beta amyloid that builds up in the brains of people living with the disease. But will this new drug be able to achieve its potential?

* Note: Lecanemab was approved in early January by the US Food and Drug Administration for the treatment of Alzheimer’s disease and will be sold under the name Leqembi.

Lecanemab is the first drug that could slow the progression of Alzheimer’s disease. Photo by Christina Victoria Craft.

Ageing populations and the need for better dementia care

How many people are affected by Alzheimer’s disease, and thus how many might stand to benefit from lecanemab? Currently, it is estimated that 55 million people live with dementia worldwide, a number which is expected to rise to 78 million by 2030. Alzheimer’s disease is the most common form of dementia and is estimated to account for around 60-80% of dementia cases. Given the proportion of older people is rising in almost every country, the increasing burden of dementia and Alzheimer’s disease represents a growing challenge to healthcare systems worldwide.

Lecanemab – a silver bullet for Alzheimer’s disease?

Lecanemab is the first drug that could actually slow the progression of Alzheimer’s disease, rather than just alleviate symptoms. Lecanemab, an antibody, works by finding and removing amyloid, a protein that accumulates and forms plaques in the brains of those with Alzheimer’s disease. Previous antibody drugs targeting the removal or amyloid show mixed results at best, or have simply not worked. In fact, even the drug’s site of action is a point of contention: the role of amyloid in Alzheimer’s disease is debated, as some have suggested that the depletion of amyloid could be more harmful than the plaques.

However, just 6 months into a Phase 3 clinical trial, lecanemab showed statistically significant disease modifier effects. 18 months in, at the end of the treatment period, lecanemab treatment reduced clinical decline (measured by a global cognitive and functional scale, CDR-SB). If these effects remain stable for over 18 months, a patient with mild cognitive impairment who might have had six years of independent life without treatment, might gain an extra 19 months with lecanemab. Despite these exciting results, the new drug has also been met with scepticism. Some are calling attention to the fact that this new drug only has a mild effect. Researchers are also highlighting the side-effects of the drug (including brain bleeds) and concerns for the drug’s safety.

Whilst understanding the efficacy and side-effects of the drug is important for answering the question of whether lecanemab can achieve its potential to help sufferers of early stage Alzheimer’s disease, this article will now take a step back and look at systemic reasons for why this drug could succeed – or fail.

The increasing burden of dementia and Alzheimer’s disease represents a growing challenge to healthcare systems worldwide. Photo by Eduardo Barrios.

The early stages of Alzheimer’s disease 

First, she became that bit more irritable. Where she would have reacted with kindness before, she was now quick to anger. Yes, she would fumble around looking for the occasional word, but it wasn’t that bad – we all forget words sometimes, right? A couple of years later, the memory loss is now undeniable. She forgets that she had lunch just an hour before. She doesn’t recognise her home of 30 years. She’s still recognising us – but for how long?

This is a familiar story for many. It’s not always anger, though. Our loved ones might become more withdrawn, anxious, apathetic, or depressed. Whilst the early signs of dementia cannot be reduced to one symptom, a common thread for both the person with dementia and their loved ones is the experience of living with uncertainty. This uncertainty – whether about what one’s own symptoms mean or about dementia itself – can delay help-seeking and ultimately a diagnosis, often up to a year or more. Delays might mean that Alzheimer’s disease is only diagnosed once it has moved into the mid or late stages – too late for treatment with lecanemab. Indeed, lecanemab has only been tested for the treatment of the early stage of Alzheimer’s disease, which encompasses mild cognitive impairment and mild Alzheimer’s disease. Moreover, the prescription of lecanemab will rely on the specific diagnostic tests, namely a PET scan or a lumbar puncture that retrieves cerebral spinal fluid, which can check for amyloid markers in the brain. Currently, only 1-2% of people with Alzheimer’s are given these tests in the UK. Moreover, some people don’t even get a diagnosis; in the UK, for example, it is estimated that the mean dementia diagnosis rate hovers around 60%. If people with Alzheimer’s disease are not receiving the appropriate tests, or only being diagnosed once they enter the later stages of disease, or not being diagnosed at all, they would not be prescribed lecanemab. So without improving the rate of diagnosis of early stage Alzheimer’s disease, how will lecanemab reach the people who would benefit from it?

Achieving early diagnosis: what do we need?

For lecanemab to reach the people it can help the most, we would need a restructuring of dementia services. A restructuring that involves not just the implementation of diagnostic tests for all those with suspected Alzheimer’s disease, but also broader public health initiatives that would increase the rate of early diagnoses. For instance, public education about dementia can help people recognise the wide range of dementia symptoms and seek support from healthcare earlier. To achieve earlier diagnoses also requires us to address the stigma around memory impairment and dementia, since fear can prevent people from seeking help.

Fortunately, some work is already being done to reduce stigma and educate the public about dementia. For example, several countries worldwide have ‘Dementia Friend’ initiatives (e.g., the UK, Denmark). These services teach people what it is like to live with dementia and help organisations take action to become more dementia-friendly. Take the example of a supermarket: if employees are more aware of dementia, they might be able to better understand and help someone with dementia in the store, rather than stigmatising them, and also be able to recognise signs of dementia in their own loved ones. The need for public health initiatives like these has been acknowledged by the World Health Organisation (WHO). The WHO’s Global Action Plan on Dementia aims for all countries to have a public awareness campaign on dementia by 2025, and for 50% of countries to have a dementia-friendly initiative, thereby building a more dementia-inclusive society.

The journey to a dementia diagnosis is complicated, tinged with uncertainty and littered with various actors (friends, family, colleagues, healthcare professionals) who have the chance to hinder or enhance the process. Therefore, it is on all of us to combat the stigma around dementia, get to know the symptoms of Azheimer’s disease and other forms of dementia, and to become dementia friends. And thus, pharmacological innovation alone will not be enough: we need public health initiatives to help move the dial towards less stigma and earlier diagnosis. Lecanemab will only reach the people who need it if we all play our part.

What’s the difference between dementia and Alzheimer’s disease?
Dementia is an umbrella term, encompassing a range of diseases that affect cognitive function. Alzheimer’s disease is the most common form of dementia and is estimated to account for around 60-80% of dementia cases. Whilst lecanemab is only pitted as an effective treatment for early stage Alzheimer’s disease, I have occasionally referred to dementia, often in reference to care services and research which address different forms of dementia together rather than Alzheimer’s disease specifically.

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