Alzheimer's drug slows mental decline by 35%

New drug allows those with Alzheimer's to keep their independence for longer
21 July 2023

Interview with 

Bart de Strooper, UK Dementia Research Institute & Richard Oakley, Alzheimer's Society


The phase 3 trial results of a new drug called donanemab has been hailed as a “turning point” in the fight against Alzheimer’s disease. Scientists say that the drug - which slowed cognitive decline by 35% on average - allows people with Alzheimer’s to keep their independence for longer. It targets the build up in the brain of the chemical beta amyloid, which is thought to poison nerve cells and cause cognitive decline in people with the condition. Bart de Strooper is an Alzheimer’s specialist and director of the UK Dementia Research Institute.

Bart - These are antibodies which you inject in the blood, and then they go into the brain and there they attack amyloid plaques and they make the brain clear this amyloid. So in a couple of months you will already see this plaque disappearing. And the really big news is that now for the first time patients which were treated with this medication were followed for two years and we see that they get partially protected against dementia. The process is clearly slowed down 30 to 40%.

Chris - And how were these people medicated? What was the nature of the administration of these antibodies? How often, how much to whom, et cetera?

Bart - They needed an infusion in their veins every four weeks. And that has been done for up to one year. And in some cases up to two years. People were then followed every half year with a new brain scan to see whether the amyloid plaques disappeared.

Chris - And do we know these antibodies actually get into the brain or could the antibodies be doing something else around the body and that triggers the brain to clean itself up? Do we really believe what we think is the mechanism we put the antibodies in, they go into the brain, and they then do the clear up.

Bart - It's a very good question. The problem is that only half a percent of what is injected gets finally in the brain. It binds there to the amyloid plaques, and what I personally think and some other researchers also, is that these antibodies recruit other cells in the brain to help with the cleaning. And these other cells are microglia. These are kind of inflammatory cells, and they go to the plaque where these antibodies are and help to clear those plaques. We think that's the mechanism.

Chris - The individuals who were studied already had some semblance of Alzheimer type change in their brain and in their cognition. Does this argue then that maybe we're at the thin end of the wedge and if we'd started sooner in people whom by some route we could identify as at high risk, potentially the gains would be even bigger?

Bart - I honestly think that that would be the case. Also in the trial as it was presented here, patients which were in an earlier phase of the disease, responded better than the ones which were later in the disease. So I think that we can gain a lot there. It's clear that we should do a big effort to diagnose patients even before they have symptoms you can see in the clinic. So we'll need blood biomarkers or we'll need brain scans and be also much more sensitive. If people start to complain about their memory, we should immediately go further and try to make a correct diagnosis.

Chris - When they said that they could slow the process down by about 30% or so, is that a clinically significant difference? Does it really make a difference to a person's outcome? Or is this a very expensive way of buying someone? A very limited amount of time.

Bart - That becomes a subjective discussion, right? There's a certain risk with the drug and there is no guarantee. People will respond differently, but 30% is the mean. There were 20% more patients which got stabilised on the drug than in the placebo. A year of stabilisation, I think that's really a lot. And so you also need to compare it with other diseases. For cancer, we don't even ask that question. We think it's absolutely normal that you want to try to survive a couple of months longer or a year longer. And it's just by doing that, that we have improved and improved and that nowadays some people live a long life with cancer and I think that will happen also with this type of medications.

Chris - Well let’s dwell a bit more on those clinical impacts and the cost-benefit equation for drugs like donanemab. Richard Oakley is head of research and innovation at the Alzheimer's Society.

Richard - What the data indicates is that by removing this protein so quickly, in fact over 18 months of the trial, the drug removes so much of the protein, the people wouldn't have been able to go on the trial anymore because it's so little. So it's really effective at removing it. And what they estimate is that it gives you about seven months-ish more time of good quality of life. So it slows down the progression of disease enough. You get seven more months of quality of life where you do remember your family, where you do play your sport, hobbies on the weekend, you can still drive, and you can still manage your own finances. So at the moment, we're looking at about a seven month delay. In terms of the progression of the symptoms.

Chris - This is a phase three trial, which is almost the final gateway before the regulator says, 'well okay, we can begin to use this in the population.' The next step will be to weigh up whether or not this is judged to be cost effective. What's your feeling about that? Are they likely to give this the rubber stamp?

Richard - So you're absolutely right. This is phase three, the final step. It now goes to the regulators and in the UK we have two, we have something called the MHRA and they'll look at the data again and say whether the drug is effective and whether it is safe enough to give to people. And then NICE looks at it and says whether we can afford to give it within our healthcare system, we should expect that decision at the end of 2024, early 2025. So we're really excited about allowing that process to happen.

Chris - But which way do you think it's going to go? Because these drugs are not going to be cheap, are they? They are going to be expensive and the health economists are going to have to weigh up buying people improved quality of life for a matter of months versus potentially doing a number of hip replacements and restoring complete quality of life to somebody who gets that rather than this anti Alzheimer's agent.

Richard - Yeah, I mean there's a lot of things to consider. I mean, in terms of the cost of the actual drug in the USA, this drug has been licensed for $25,000 per person per year. So I don't think that is a prohibitive number. I think the bigger question that the health economists absolutely need to look at is the infrastructure around giving these treatments. So we already know only 2% of people currently get the type of early and accurate diagnosis that you need in order to benefit from these drugs. So we need to prove very early on they have Alzheimer's disease and they have to build up this sticky protein, this amyloid in their brain. So a lot of the consideration is, well actually we need to really change the infrastructure of our health service to enable us to work out who can get this treatment, who will benefit from it. I'm hopeful that those regulators will look at the data and conclude that it is safe, effective, and cost effective. These are the first ever disease modifying treatments that actually slow down the progression of Alzheimer's disease, which is the cause of 60% of all dementias in the UK, which is one of the biggest killers in the uk. So I'm hopeful that this will begin a whole new era and then we'll start to see things happening. But I think it's really important that we allow those authorities to make their own decision based on the data they will see.

Chris - David Cameron, our former prime Minister, was making a point earlier in the week that in fact, if you look at how many people are destined to be affected by Alzheimer's disease in the years ahead, and then you work out what the complex care needs for those people are, that in fact if you give people longer and more independence for longer, then it almost pays for itself to an extent.

Richard - There are many, many positives and we've talked about this being the beginning of a whole new era because disease modifying treatments are coming and we believe this would lead to a change in the health and the care system. So I think long term there are an awful lot of benefits and I don't think anyone can debate that. The question I think regulators will look at is, in the short term, do we have the infrastructure to change in order to take advantage of this situation?


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