Some hailed 2023 as the beginning of a turning point in our efforts to combat Alzheimerās disease. Two countries ā the US and Japan ā approved a drug called lecanemab, the first treatment that actually slows the conditionās progression, rather than just easing its symptoms. Many other countries, including the UK and Australia, are now considering following suit, but the drug isnāt without its critics.
Lecanemab gained approval in the US and Japan after a trial showed it slowed the rate of cognitive decline by 27 per cent over 18 months among people with early-stage Alzheimerās, compared with a placebo.
It certainly sounds impressive, but a closer look shows that this figure comes from just a 0.5-point difference on an 18-point dementia symptom scale between lecanemab and a placebo: those who received the drug worsened by 1.2 points versus 1.7 points.
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āThe magnitude was to a point that many say it doesnāt make any clinical difference,ā says at the University of California, San Francisco. A later trial for a similar medication called donanemab, which isnāt yet approved anywhere, , based on a 0.7-point difference between the drug and placebo groups.
Nevertheless, rather than lecanemab just somewhat decelerating a loss of cognition among people with Alzheimerās, surveys show that their decline in quality of life also slowed by about 50 per cent. āIt essentially means that for daily activities, people maintain their independence longer,ā says at Eisai, lecanemabās manufacturer. A spokesperson for donanemabās manufacturer, Lilly, says that giving people the opportunity to continue doing these daily activities for longer is clinically meaningful.
The drugsā mechanisms of action also help to reinforce the āamyloid hypothesisā, which proposes that an abnormal build-up of the protein amyloid leads to plaques that are toxic to brain cells, resulting in Alzheimerās symptoms.
Targeting amyloid has long been suggested as an Alzheimerās treatment, but a series of trial failures led some to question whether these plaques really drive the condition after all. Eyebrows were also raised in 2021 when the US approved a drug called aducanumab on the basis it reduces amyloid plaques, despite this not translating into symptom improvement.
Like aducanumab, lecanemab binds to these plaques in the brains of people with Alzheimerās, activating an immune response that clears them. At the end of lecanemabās trial, brain scans showed , which may be responsible for its cognitive-slowing properties, however limited they may be.
Unlike some of the trials that have failed, lecanemabās studies specifically focused on people with early-stage Alzheimerās. It is probably too late for amyloid clearance to make a significant impact once a certain level of neurodegeneration occurs, says Irizarry.
Lecanemab doesnāt halt Alzheimerās progression or reverse its effects ā people on the drug still experience cognitive decline, which suggests that factors other than amyloid are involved in the condition to some degree.
But their decline is slower than what would otherwise be expected, and with other treatments only slightly mitigating symptoms, some people may consider any amount of slowed cognitive decline better than none.
Efficacy aside, safety concerns have also been raised, including a heightened risk of brain bleeding, swelling and inflammation, . An Eisai spokesperson says these deaths canāt definitely be attributed to the drug. The majority of lecanemabās brain-related side effects arenāt serious and resolved within four months in a late-stage trial, says Grinberg.
Overall, at Alzheimerās Research UK says the drug is ānot perfectā, but some people, such as those without a personal or family history of brain bleeding, may consider its benefits worth the risks.
But there is also the issue of cost, particularly in the UK where treatments are only introduced if they are judged to provide value for money. Lecanemab is administered via regular costly infusions. Recipients also need regular brain scans to check for potentially dangerous side effects.
Only showing efficacy in early-stage Alzheimerās raises further questions about its practicalities, as the condition is often spotted at a more advanced stage, though new tools to diagnose the condition earlier are potentially on the horizon.
Despite lecanemabās shortcomings, its ability to slow cognitive decline in people with Alzheimerās ā even if just to a small degree ā is generally considered a step in the right direction when it comes to treating such a complicated condition.
āTen years ago or even five years ago, we were hearing people say, āAlzheimerās is just an inevitable part of ageing; there is nothing you can do about itā,ā says Kohlhaas. āNow, we can show that you can do something about it.ā
