Alzheimer’s drugs may not reduce dementia deaths, scientists warn

Debate over whether the benefit of the treatments outweighs the high costs and risk of severe side effects such as shrinking brain matter

Alzheimer’s drugs that claim to slow down the progression of the disease may not be able to reduce the number of deaths from dementia, Cambridge scientists have said.
Two heralded treatments for Alzheimer’s have emerged in recent years with data showing they slow the cognitive impairment caused by the disease, which is the UK’s biggest killer.
However, scientists have been locked in debate over whether the benefit of the drugs outweighs the substantial financial costs and high risk of severe side effects such as shrinking brain matter and brain bleeds.
Now, scientists from the University of Cambridge have penned a perspective article published in the journal Alzheimer’s and Dementia warning that “it is far from clear” whether these drugs can “ever significantly reduce population-level dementia morbidity at scale”.
The letter is a significant intervention in the ongoing conversation over the drugs, with advocates in favour of approving and administering the treatments saying they could pave the way for other, more powerful versions which could finally cure dementia. Critics, however, say the risks are too great, and the benefits imperceivable in reality.
The drugs, lecanemab and donanemab, work by clearing out amyloid in the brain. Amyloid is the protein that aggregates on neurons and stops the brain working properly, causing dementia.
Both the drugs cost around £20,000 a year and are given in hospital as an intravenous drip, a process that takes about an hour, with lecanemab given every fortnight and donanemab once a month.
Data from trials run by the companies making the drugs, Eisai and Eli Lilly, respectively, show a 27 per cent and 35 per cent slowing of cognitive decline in people with early stage Alzheimer’s, compared with a placebo.
Neither of the drugs has been approved in the UK and the European medicine regulators last month said the benefits of lecanemab did not counterbalance the risk of serious side effects and rejected its licence. Lecanemab and donanemab are available in the US after being granted approval by the FDA.
But scientists are now increasingly claiming that while the headline data indicates a significant effect size, the impact of the drugs is so small it would not be recognisable by a doctor or the patient.
Dr Madhav Thambisetty, a senior clinical investigator at the US National Institute on Aging, spoke at one of the largest scientific conferences in the world earlier this year and warned that some participants in the study trials of the drugs lost up to three teaspoons of brain volume.
There have also been calls for the drug manufacturers to be more transparent with their data and provide more long-term information to the public about these drugs.
Doctors have also warned that just two per cent of eligible people with early signs of Alzheimer’s will be able to receive the drug due to the need for specialist PET brain scans which are not routinely available.
The Cambridge scientists say that the price of the drugs, the demands on the patient and health service in the administering of the treatment, and the high risk of side effects, make the potential roll out of the treatments “extremely challenging for even the best-funded healthcare systems”.
Jen Keen, head of policy at Alzheimer’s Society, says the two drugs “are not a cure [but] they are a part of the puzzle”.
“Despite the issues raised in this research, we remain at an important and exciting moment for dementia. Scientists are learning more all the time about Alzheimer’s disease and our ability to slow it down,” she added.
“There are currently 164 active clinical trials for Alzheimer’s disease and we expect more treatments to be submitted for regulatory approval in the future.”
A spokesman for donanemab manufacturer Eli Lilly said: “Any new treatments are reviewed by the MHRA (Medicines and Healthcare products Regulatory Agency) and would subsequently be considered by Nice (National Institute for Health and Care Excellence) to determine clinical and cost-effectiveness and patient eligibility.
“Access to any new medicine will also depend on the appropriate diagnostic and treatment pathway being available for healthcare professionals and patients.
“Lilly is committed to partnering with the NHS and regulatory bodies to ensure new innovations can reach the people that need them.”
Eisai has been approached for comment.