Researchers have hailed the dawn of a new era of therapies for Alzheimer’s disease after a clinical trial confirmed that a drug slows cognitive decline in patients in the early stages of the disease.
The result comes after decades of failure in the field and has encouraged experts to say that Alzheimer’s disease – which affects 30 million people worldwide – may be treatable.
“This is the first drug that offers a real treatment option for patients with Alzheimer’s disease,” said Bart De Strooper, director of the UK Dementia Research Institute at University College London. .
“Although the clinical benefits seem somewhat limited, they can be expected to become more apparent over time.”
The drug, lecanemab, is an antibody therapy that breaks down clumps of proteins called amyloid beta that build up in the brain.
It’s unclear to what extent the clusters cause Alzheimer’s disease, but in patients with inherited forms of the disease, they appear to set the stage for a cascade of brain changes that regularly destroy brain cells. .
The developers of Lecanemab, Biogen in the United States and Eisai in Japan, announced the first results of the clinical trial in nearly 1,800 patients in September, but researchers in the field have been eagerly awaiting the full data, which has was published Tuesday in the New England of Journal of Medicine.
This showed that the drug reduced the decline in patients’ overall mental abilities by 27% over 18 months – a modest but significant result.
“I believe this confirms a new era of modification in Alzheimer’s disease. An era that comes after more than 20 years of hard work on amyloid immunotherapies, by many people and many disappointments along the way,” said Nick Fox, professor of clinical neurology and director of the Center for Amyloid Research. dementia at UCL.
Alzheimer’s disease accounts for nearly two-thirds of the 55 million people with dementia worldwide. It is the leading cause of death in the UK: patients usually die within seven years of diagnosis.
The disease costs the UK £25billion a year, a number set to nearly double to £47billion by 2050. The most common first signs are memory problems, but as the disease progresses, people may find themselves lost in familiar places, having difficulty making decisions. , struggling with simple chores and eventually unable to eat or move around without help.
For decades, efforts to slow, halt or reverse the disease have failed, costing pharmaceutical companies billions of dollars and forcing some to abandon the field altogether. Many drugs have shown no benefit in trials because they hit the wrong molecular target or were tested in patients whose disease was too advanced. The positive results of lecanemab should lead to a new generation of drugs offering better and better control of the disease.
Amid widespread excitement over the results, the researchers highlighted a host of issues that could impede the drug’s uptake.
Lecanemab is expensive – between £10,000 and £30,000 per patient per year – and has such a modest effect, at least over 18 months, that it is unclear whether patients would notice any benefit.
It is unclear when, or even if, it will be approved by the UK Medicines and Health Products Regulatory Agency and the National Institute for Health and Care Excellence (Nice).
Another major obstacle 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 all 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 bleeding.
Questions have been raised about the drug’s safety after two deaths during the trial were linked to the drug by some researchers.
According to the published report, 13 people died during the trial, six who received the drug and seven who received the placebo. The report says none of the deaths were considered by investigators to be drug-related.
“Lecanemab is not a panacea, but it provides proof of concept that Alzheimer’s disease is not an impossible problem: it is potentially treatable and maybe even one day preventable,” said Jonathan Schott, Professor in Neurology at UCL and Medical Director of Alzheimer’s Research UK. .
“We need to expand our research and continue to study 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 Center for Discovery Brain Sciences at the University of Edinburgh, said that while the results were “good news”, it was important to note that lecanemab is not not a cure for Alzheimer’s disease.
“Both groups in the trial had worsening symptoms, but people taking the drug didn’t experience diminished cognitive abilities as much,” she said. “As the authors point out, there is no accepted definition of clinically significant effects in the cognitive test they used, and it is not yet clear whether the modest reduction in decline will make a big difference for people with dementia.”
Dr Richard Oakley of the Alzheimer Society said the findings could be “game changing”.
“There is still a long way to go before we can see lecanemab available on the NHS, and we await clarification on how and when the approval process will take place in the UK, and whether regulators think that it is profitable. It should be remembered that lecanemab can only be given to people with early stage Alzheimer’s disease who have amyloid in the brain. This means that people with other types of dementia, or in the later stages of Alzheimer’s disease, may not benefit from this drug.
