An experimental drug has slowed the rate of memory and thinking decline in people with early Alzheimer’s disease in what is being described as a “landmark moment” for dementia treatment.
The cognition of Alzheimer’s patients who received the drug, developed by Eisai and Biogen, declined 27% less than those who received a placebo treatment after 18 months. This is a modest change in clinical outcome, but it is the first time that a drug has been clearly shown to alter the trajectory of the disease.
“This is a landmark moment for dementia research, as it is the first phase 3 trial of an Alzheimer’s drug in a generation to successfully slow cognitive decline,” said Dr. Susan Kohlhaas, director of research from Alzheimer’s Research UK. “Many people feel that Alzheimer’s is an inevitable part of aging. This spells it out: if you intervene early, you can have an impact on people’s progress.”
In the study, which enrolled about 1,800 patients with early-stage Alzheimer’s, patients received twice-weekly infusions of the drug, called lecanemab. It was also shown to reduce toxic plaques in the brain and slow the decline in memory and the ability of patients to perform everyday tasks.
About a fifth of patients experienced side effects, such as brain swelling or brain hemorrhage visible on PET scans, and about 3% of those patients experienced symptomatic side effects.
The results offer a boost to the “amyloid hypothesis,” which hypothesizes that the sticky plaques seen in the brains of dementia patients play a role in damaging brain cells and causing cognitive decline.
A number of earlier drug candidates had been shown to successfully reduce amyloid levels in the brain, but without any improvement in clinical outcomes, leading some to question whether the research field had been on the wrong track.
Rob Howard, Professor of Old Age Psychiatry at University College London (UCL), said: “This is an unequivocally positive result statistically and represents a historic moment where we see the first convincing modification of Alzheimer’s disease. Alzheimer’s. God knows we’ve waited long enough for this.”
Eisai and Biogen are expected to apply for regulatory approval in the US and Europe by the end of the year. If approved, health care providers will face difficult decisions about whether to fund the drug, which requires infusions every two weeks, and who will be eligible to receive it because the clinical improvements seen by patients are just below a widely accepted benchmark. .
On a 14-point scale used to assess the progression of Alzheimer’s disease, patients who received the drug scored 0.45 higher than those who received placebo treatment, and a patient with Alzheimer’s disease was expected to decrease by about 1 point per year.
Howard said: “The minimum accepted valid difference is between 0.5 and 1.0 points, [meaning] that there will be some very difficult conversations and decisions in the coming weeks and months.”
Overall benefits will depend on whether patients taking the drug maintain a better trajectory beyond the first 18 months, but the latest data can’t answer that question.
There are also questions about whether the drug could slowly taper off at an even earlier stage. Eisai is recruiting people at high risk for Alzheimer’s who haven’t yet developed symptoms for more trials to try to help answer this question.
The prospect of an effective therapy for Alzheimer’s will focus attention on the ability of healthcare services to treat the nearly 1 million people affected in the UK, one in 14 people over the age of 65.
According to Alzheimer’s Research UK, only one in three psychiatric services would be ready to provide a new treatment within a year and, in the UK, many patients are diagnosed at a much later stage than those who participated in the latest trial.
“This will require a sea change in the way we deliver our services,” said Professor Jon Schott, Medical Director of Alzheimer’s Research UK and Professor of Neurology at UCL.
“If this is licensed and goes through Nice [the National Institute for Health and Care Excellence], the demand will be huge. We are not ready to deliver this on a large scale and we need to address it now.”