New Alzheimer’s Drug

The news that the new Alzheimer’s drug Lecanemab not only removed plaques on the brain in clinical trials but also slowed patients’ mental decline burst like a Christmas star into the weary world of Alzheimer’s. It was the first positive results after decades of failure and was hailed by the Alzheimer’s Society as a momentous breakthrough. But examining the data raises two important findings that dim the star-shine and are giving cause for concern – patients’ cognitive improvement is very small (only .45 on a scale measuring 0 to 18) and its effect on patients’ lives is debatable. Also, some patients experienced significant side effects, with two reported deaths. A leading expert worries how individuals with Alzheimer’s and their families, who are desperate for treatments, will weigh the two sides if Lecanemab is approved by regulatory agencies.

The drug has been developed by pharmaceutical company Eisai, based in Tokyo, and biotechnology firm Biogen, based in Cambridge, Massachusetts. The trial included 1795 participants with either mild cognitive impairment (MCI) or early stage Alzheimer’s. Half of them took Lecanemab and the other half a placebo. Lecanemab attacks the beta amyloid (amyloid B) deposits that build up in the brains of people with Alzheimer's, thought by some scientists to be the cause of the disease. Patients given placebo saw their Alzheimer’s progression scores increase by an average of 1.66 points over the eighteen month period, while those given Lecanemab saw just 1.21 point increase. Eisai said that this represents a 27% slowing in cognitive decline, but on the cognitive abilities’ measurement scale, called the Clinical Dementia Rating–Sum of Boxes (CDR–SB) of 0 to 18, the clinical benefit of an 0.45 point difference has been questioned.

‘It’s a modest benefit,’ said Brent Forrester, director of the geriatric psychiatry research programme at McLean Hospital in Belmont Massachusetts, who helped to run the clinical trial for Lecanemab. He is concerned about safety; about 20% of people taking Lecanemab had brain-scan anomalies that indicated swelling or bleeding. This represents just 1.4% of the treatment group, but Rob Howard, psychiatrist at University College London who specialises in dementia, said ‘that’s not a trivial risk profile’. He suspects that the lack of demonstrable clinical effectiveness will mean that Lecanemab will not be taken up widely within healthcare systems around the world, ’although there will always be those whose heart rules their head.’ (Click here for more)

Professor Brent Forrester is also concerned that Lecanemab could be given to people who are in the early stages of Alzheimer’s disease and have not experienced cognitive decline and experience complications which could worsen their quality of life. But an Eisai/Biogen study called ‘Ahead’ is already testing Lecanemab in people who are not exhibiting any signs of Alzheimer’, but have the plaques of amyloid build up in the brain.

The amyloid B hypothesis is contentious, and many scientists are sceptical. Amyloid is ‘associated with the problem, but it isn’t ‘the’ problem’, says George Perry, a neurobiologist at the University of Texas at San Antonio and a sceptic of the amyloid hypothesis. ‘If you modulate it, of course you can have some small benefit.’ Nature magazine recently published a study by researchers at Yale University showing why the patches of protein seem relevant without necessarily being directly responsible.

Other studies show that 30% of older people have the deposits in the brains, but do not develop Alzheimer’s. An example was Sister Mary, in the ‘Nuns’ Study’ who had high cognitive test scores before her death at 101 years of age. Autopsy showed that her brain carried abundant neurofibrillary tangles and amyloid plaques. With around 175 research projects currently undergoing, we can expect more clarity and understanding