An experimental drug has slowed the rate of decline in memory and thinking in people with early Alzheimer’s disease in what is being described as a “historic moment” for dementia treatment.
The cognition of Alzheimer’s patients given the drug, developed by Eisai and Biogen, declined by 27% less than those on a placebo treatment after 18 months. This is a modest change in clinical outcome but it is the first time any drug has been clearly shown to alter the disease’s trajectory.
“This is a historic moment for dementia research, as this is the first phase 3 trial of an Alzheimer’s drug in a generation to successfully slow cognitive decline,” said Dr Susan Kohlhaas, the director of research at Alzheimer’s Research UK. “Many people feel Alzheimer’s is an inevitable part of ageing. This spells it out: if you intervene early you can make an impact on how people progress.”
In the study, which enrolled roughly 1,800 patients with early stage Alzheimer’s, patients were given twice-weekly infusions of the drug, called lecanemab. It was also shown to reduce toxic plaques in the brain and slow patients’ memory decline and ability to perform day-to-day tasks.
About a fifth of patients experienced side-effects, including brain swelling or brain bleeding visible on PET scans, with about 3% of those patients experiencing symptomatic side-effects.
The results offer a boost to the “amyloid hypothesis”, which assumes that sticky plaques seen in the brains of dementia patients play a role in damaging brain cells and causing cognitive decline.
A series of previous drug candidates had been shown to successfully reduce levels of amyloid 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, a professor of old age psychiatry at University College London (UCL), said: “This is an unambiguously statistically positive result and represents something of an historic moment when we see the first convincing modification of Alzheimer’s disease. 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, healthcare providers will have difficult decisions about whether to fund the drug, which requires infusions every two weeks, and who will be eligible for it because the clinical improvements seen by patients fall just below a widely accepted benchmark.
On a 14-point scale used to assess Alzheimer’s progression, patients on the drug scored 0.45 higher than those on the placebo treatment, with an Alzheimer’s patient being expected to decline by about 1 point a year.
Howard said: “The accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, [meaning] that there are going to be some very difficult conversations and decisions in the next weeks and months.”
The overall benefits will depend on whether patients on the drug maintain a better trajectory beyond the first 18 months, but the latest data cannot answer that question.
There are also questions about whether the drug could slow decline at an even earlier stage. Eisai is recruiting people with a high risk of Alzheimer’s who have not yet developed symptoms to take part in further trials to try to help answer this.
The prospect of an effective Alzheimer’s therapy will focus attention on the ability of healthcare services to deliver treatments to the almost 1 million people affected in the UK – one in every 14 people aged 65 years and over.
According to Alzheimer’s Research UK, only one in three psychiatry services would be ready to deliver a new treatment within a year and, in the UK, many patients are diagnosed at a much later stage than those who took part in the latest trial.
“This will require a radical change in how we deliver our services,” said Prof Jon Schott, the chief medical officer of Alzheimer’s Research UK and a professor of neurology at UCL.
“If this is licensed and this gets through Nice [the National Institute for Health and Care Excellence], the demand will be huge. We’re not ready to deliver this at scale and we need to address that now.”