Eisai and Biogen announce Alzheimer's drug trial results

Partner companies Eisai and Biogen have recently announced promising clinical trial results for their new Alzheimer’s drug lecanemab. Over 18 months, patients treated with lecanemab experienced slower symptom progression than the placebo group.

“What actually causes Alzheimer’s disease is not really known… There’s some debate about how and when these processes happen,” said Scientia Professor Henry Brodaty AO, Co-Director of the Centre for Healthy Brain Ageing (CHeBA) at UNSW Sydney.

One of the prime suspects is a protein fragment called beta-amyloid, which is quite sticky and can accumulate in clumps in the brain, called ‘amyloid plaques’. These clumps of protein build up around neurons.

Amyloid is directly toxic to brain cells, and also promotes the development of the other main brain pathology — neurofibrillary tangles in brain cells. The tangles are made of tau proteins that get knotted up inside neurons, blocking function and causing toxicity. Plaques also lead to the development of inflammation in the brain.

Most of the current Alzheimer’s drugs help to manage symptoms but can’t halt or reverse brain degeneration. They mainly work by maintaining levels of neurotransmitters that can be decreased in patients with Alzheimer’s.

“Research into Alzheimer’s treatments in the ’80s came up with the only current drugs on the market,” said Professor Peter Schofield AO, the CEO of Neuroscience Research Australia (NeuRA) and professor at UNSW Medicine & Health.

“They’re not targeting the underlying disease cause.”

In 2021, a disease-modifying Alzheimer’s drug, aducanumab, was approved for use in the US by the Food and Drug Administration (FDA) but it isn’t approved in other countries, including Australia and Europe. The FDA approval was highly controversial as clinical trials had failed to show that the drug caused an improvement in dementia symptoms, and the drug led to a degree of brain swelling and/or bleeding in up to 40% of clinical trial participants.

The new drug, lecanemab, works in a similar way but targets amyloid fibrils, which are smaller clumps of protein that eventually turn into amyloid plaques.

“Why wait until you’ve got a pile of garbage — the plaque? Why don’t you just pick up bits of litter on the way?” Schofield said.

Eisai and Biogen reported that in their latest 18-month clinical trial, symptom scores for patients treated with lecanemab had worsened 27% less compared to those given a placebo. This has been met with much excitement as, unlike aducanumab and other previous treatments, lecanemab has shown the first evidence of slowing down Alzheimer’s progression.

At the same time, the limitations of these results can’t be ignored.

Firstly, though statistically significant, the difference in symptoms between the treatment and placebo group in the trial was 0.45 points on an 18-point scale. Most clinicians in the field suggest that a greater difference is needed to impact patients’ lives, for example 1 to 2 points.

Secondly, lecanemab targets beta-amyloid build-up but there are probably other contributors to Alzheimer’s progression — for example neurofibrillary tangles. These other changes would not be fixed with this drug.

It also must be acknowledged that lecanemab causes the potentially serious side effects of brain swelling and bleeding. In this recent clinical trial, 21% of the treatment group versus 9% of the placebo group experienced these changes on brain MRI scan.

Finally, Alzheimer’s disease is only one of many causes of dementia, so lecanemab won’t be of benefit to those with other causes, for example vascular changes and Parkinson’s disease. In very old people with more severe dementia, there are often multiple contributing factors. The lecanemab trial did not focus on this patient group — the drug’s impact was only tested in those with early or mild dementia caused by Alzheimer’s.

Despite all these caveats, these latest findings are a significant step forward for Alzheimer’s research, according to the partner companies.

“We still have a long way to go until we have what everyone wants. A treatment for Alzheimer’s for themselves, their loved one, their parent, that is affordable and efficacious,” Schofield said.

“But it looks like we’ve got a first foot on the ladder.”

Image credit: iStock.com/Ildar Imashev