Researchers have hailed the dawn of a new era of Alzheimer’s therapies after a clinical trial confirmed that a drug slows cognitive decline in patients with early stages of the disease.
The result comes after decades of failure in the field and encouraged experts to say Alzheimer’s – which affects 30 million people worldwide – could be treatable.
“This is the first drug that provides a real treatment option for Alzheimer patients,” said Bart De Strooper, director of the UK Dementia Research Institute at University College London.
“While the clinical benefits appear somewhat limited, it can be expected that they will become more apparent over time.”
The drug, lecanemab, is an antibody therapy that removes clumps of protein called beta amyloid which builds up in the brain.
It is unclear how much the clumps drive Alzheimer’s, but in patients with inherited forms of the disease, they appear to pave the way for a cascade of brain changes that steadily destroy brain cells.
Lecanemab’s developers, Biogen in the US and Eisai in Japan, announced top line results from the clinical trial in nearly 1,800 patients in September, but researchers in the field have anxiously awaited the full data, which were published on Tuesday in the New England of Journal of Medicine.
This showed the drug reducing the decline in patients’ overall mental skills by 27% over 18 months – a modest but significant result.
“I believe it confirms a new era of disease modification for Alzheimer’s disease. An era that comes after more than 20 years of hard work on anti-amyloid immunotherapies, by many, many people, and many disappointments along the way,” said Nick Fox, professor of clinical neurology and director of the Dementia Research Centre at UCL.
Alzheimer’s accounts for nearly two-thirds of the 55 million people living with dementia worldwide. It is the leading cause of death in the UK: patients typically die within seven years of a diagnosis.
The condition costs the UK £25bn a year, a number expected to nearly double to £47bn by 2050. The most common early signs are memory problems, but as the disease progresses, people can find themselves lost in familiar places, having trouble with decisions, struggling with simple tasks, and ultimately unable to eat or move without help.
For decades, efforts to slow, halt or reverse the disease have failed, costing pharmaceutical companies billions of dollars and forcing some to leave the field altogether. Many drugs showed no benefit in trials because they hit the wrong molecular target or were tested in patients whose disease was too advanced. The positive results from lecanemab are expected to lead to a new generation of drugs that offer better and better control of the disease.
Amid widespread excitement at the results, researchers highlighted a host of issues that could hamper the drug’s adoption.
Lecanemab is expensive – between £10,000 and £30,000 per patient a year – and has such a modest effect, at least over 18 months, that it is unclear whether patients would notice any benefit.
It is not clear when, and even whether, it will be approved by the UK’s Medicines and Healthcare products Regulatory Agency and the National Institute for Health and Care Excellence (Nice).
Another big hurdle is that the NHS is not equipped to deliver the drug: the health service lacks sufficient diagnostic tests to identify those most likely to benefit; it has too few staff to give every patients an infusion of the drug every two weeks; and it cannot provide the multiple MRI scans needed throughout treatment to check for side-effects, such as brain swelling and haemorrhages.
Questions have been raised about the drug’s safety after two deaths on the trial were linked to the drug by some researchers.
According to the published report, 13 people died on the trial, six who received the drug, and seven who received the placebo. The report states that none of the deaths were considered by investigators to be related to the drug.
“Lecanemab is not a panacea, but it provides proof of concept that Alzheimer’s is not an impossible problem: it is potentially treatable and perhaps one day even preventable,” said Jonathan Schott, professor of neurology at UCL and chief medical officer at Alzheimer’s Research UK.
“We need to expand our research, and to continue to investigate different drugs targeting different aspects of the disease: ultimately it is likely that combination therapies will be needed.”
Tara Spires-Jones, professor of neurodegeneration and deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said while the results were “good news”, it was important to note that lecanemab is not a cure for Alzheimer’s.
“Both groups in the trial had worsening symptoms, but people taking the drug did not decline as much in their cognitive skills,” she said. “As the authors point out, there is not an accepted definition of clinically meaningful effects in the cognitive test they used, and it is not clear yet whether the modest reduction in decline will make a big difference to people living with dementia.”
Dr Richard Oakley at the Alzheimer’s Society said the results could be “gamechanging”.
“There is still a long way to go before we could see lecanemab available on the NHS, and we await clarity for how and when the approval process will take place in the UK, and whether regulators believe it is cost-effective. We mustn’t forget that lecanemab can only be given to people with early Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or in the later stages of Alzheimer’s disease, can’t benefit from this drug.”
