Some hailed 2023 as the beginning of a turning point in our efforts to combat Alzheimer鈥檚 disease. Two countries 鈥� the US and Japan 鈥� approved a drug called lecanemab, the first treatment that actually slows the condition鈥檚 progression, rather than just easing its symptoms. Many other countries, including the UK and Australia, are now considering following suit, but the drug isn鈥檛 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 Alzheimer鈥檚, 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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鈥淭he magnitude was to a point that many say it doesn鈥檛 make any clinical difference,鈥� says at the University of California, San Francisco. A later trial for a similar medication called donanemab, which isn鈥檛 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 Alzheimer鈥檚, surveys show that their decline in quality of life also slowed by about 50 per cent. 鈥淚t essentially means that for daily activities, people maintain their independence longer,鈥� says at Eisai, lecanemab鈥檚 manufacturer. A spokesperson for donanemab鈥檚 manufacturer, Lilly, says that giving people the opportunity to continue doing these daily activities for longer is clinically meaningful.
The drugs鈥� mechanisms of action also help to reinforce the 鈥渁myloid hypothesis鈥�, which proposes that an abnormal build-up of the protein amyloid leads to plaques that are toxic to brain cells, resulting in Alzheimer鈥檚 symptoms.
Targeting amyloid has long been suggested as an Alzheimer鈥檚 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 Alzheimer鈥檚, activating an immune response that clears them. At the end of lecanemab鈥檚 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, lecanemab鈥檚 studies specifically focused on people with early-stage Alzheimer鈥檚. It is probably too late for amyloid clearance to make a significant impact once a certain level of neurodegeneration occurs, says Irizarry.
Lecanemab doesn鈥檛 halt Alzheimer鈥檚 progression or reverse its effects 鈥� 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 can鈥檛 definitely be attributed to the drug. The majority of lecanemab鈥檚 brain-related side effects aren鈥檛 serious and resolved within four months in a late-stage trial, says Grinberg.
Overall, at Alzheimer鈥檚 Research UK says the drug is 鈥渘ot perfect鈥�, 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 Alzheimer鈥檚 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 lecanemab鈥檚 shortcomings, its ability to slow cognitive decline in people with Alzheimer鈥檚 鈥� even if just to a small degree 鈥� is generally considered a step in the right direction when it comes to treating such a complicated condition.
鈥淭en years ago or even five years ago, we were hearing people say, 鈥楢lzheimer鈥檚 is just an inevitable part of ageing; there is nothing you can do about it鈥�,鈥� says Kohlhaas. 鈥淣ow, we can show that you can do something about it.鈥�
