A breakthrough in Alzheimer's treatment

A new drug shows promise in slowing Alheimer's progression, but not without some serious side effects...
02 December 2022

Interview with 

Charles Piller, Science Magazine

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As life expectancy rises, more people are living to an age when degenerative diseases like Alzheimer's become a problem. And in recent decades the pharmaceutical sector has been pursuing various approaches to try to slow down or halt the disease. This week the Japanese company Eisai announced the results from a phase 3 clinical trial on nearly 2000 people in the early stages of Alzheimer's comparing their new drug lecanemab against a placebo. The drug is a modified antibody that works like a sponge to soak up and reduce the build-up of a protein called "beta-amyloid" that accumulates and kills nerve cells in the brains of people with Alzheimer's. In the trial, after 18 months on the drug, participants showed a 27% slower rate of progression of their Alzheimer's symptoms, but they still worsened all the same. So it's certainly not a cure, and it's going to be a tricky call for regulators and health funders to judge whether, in this case, the pill is better than the ill, because as well as being costly, there were also some serious side effects, including fatal brain haemorrhage...

Charles - My name is Charles Piller and I'm a journalist with Science Magazine. This study that I wrote about is regarded by many as one of the most promising developments in the field in a long time. And it involves an antibody that is used to bind to certain deposits of proteins in the brain that many people think are responsible for Alzheimer's disease. And so by using this antibody, the hope is that it would arrest or even reverse eventually the effects of Alzheimer's disease. In fact, in this experiment, they found that it did not do those things, unfortunately, but they decided that it had an effect of slowing down the cognitive decline. In other words, the people who received this drug continued to decline in their cognitive abilities, but a little bit more slowly than those who had the placebo. So this, in the curious world of Alzheimer's research, is regarded as a great success. Obviously it doesn't sound like a wonderful gigantic development, but it's something people could hang their hats on.

Chris - With any drug though, there are always side effects. And in this instance, you are pointing out that there was the most dramatic side effect of all in one particular recipient.

Charles - Yes, this is a case of a woman who received this drug and after three infusions of it, she had a stroke and was treated with something called TPA, which is a very powerful anticoagulant that people are often given immediately after they have a stroke. In the vast majority of cases, it's very successful in mitigating the effects of a stroke. So she was given TPA, but what happened was the combination of lecanemab, the drug she was given in the trial and TPA combined to cause a massive brain hemorrhage and caused death in horrific circumstances. These are not my judgements about what happened. These are the judgments of the neurologists and the pathologists, the person who did the autopsy. They concluded based on their scientific analysis and on the autopsy that this is what happened.

Chris - Strokes are very common, especially in older people, as is Alzheimer's disease. So how do we know that the drug for Alzheimer's disease caused the susceptibility to this bleeding that the stroke agent caused? Is there a mechanism that would explain this?

Charles - Yeah, there is a very strong scientific mechanism. So I mentioned before that one of the characteristics of Alzheimer's disease is deposition of plaques, proteins that stick to brain cells and also to the blood vessels. What happened in this case is this woman who had the stroke also had a condition called cerebral amyloid angiopathy, and it's a condition that causes a lot of plaque to build up around these blood vessels that serve the brain. And when she was given this drug lecanemab, what scientists believe is that it stripped away a lot of those plaques, and in so doing caused those blood vessels to become inflamed and weakened and when the TPA was given, they burst.

Chris - What are the implications of this then? Is this a show stopper for lecanemab, the drug in question?

Charles - The US Food and Drug Administration here, and also your regulatory bodies will be evaluating that very question. However, what we do know is that there is long standing concern about this type of drug being used with any kind of blood thinner that had been associated with very bad brain bleeds in people who are taking this drug and similar antibody drugs for Alzheimer's disease. So we're waiting to see if the makers of this drug lecanemab are going to be suggesting to regulators that it shouldn't be given to people who are on blood thinners or who might be prescribed blood thinners in the case of a stroke. And it kind of creates a terrible dilemma for some patients. So what we don't know is what precautions could be taken and what warnings could be given. And I think we'll hear more today actually at a big meeting where the maker of the drug, Eisai, which is a Japanese company, is going to be talking about the results of their clinical trial. And I'm hoping, and many people are hoping that they will address this question of brain bleeds and blood thinners directly.

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