In 2022 the United States FDA (Food and Drug Administration) approved a new treatment called Aducanumab for Alzheimer’s disease. There was significant international controversy about that decision. It was widely reported that the scientific advisory panel of the FDA had actually recommended against approving it. Eight of them voted against it, and only one for it. In face of the FDA decision to approve it anyway, three members of that scientific panel resigned. They didn’t think it should be offered to patients because the risks outweighed any benefits.
In Alzheimer’s disease a protein called amyloid builds up in the brain. It has long been understood that its presence is toxic to brain cells, so logically, if you could stop the build-up, it would protect the brain and reduce the Alzheimer’s symptoms. The treatment is administered by an intravenous infusion, lasting about an hour, every four weeks.
Aducanumab is not available in the UK and the EMA (European Medicines Agency) decided against approval. Even though the medicine removed measurable amounts of the problem substance from the brain, it didn’t make a lot of difference to how the patient was. It didn’t show much clinical benefit to the person, and it had side effects.
Then in January 2023 the FDA in the United States gave ‘accelerated’ approval to the next new Alzheimer’s treatment. This medicine comes in the form of an intravenous infusion, given every two weeks. The “accelerated” nature of this FDA approval is a special process that is only for drugs where the condition being treated is serious and there are no other treatments. This infusion is called Lecanemab, and it seems to work in the early stages of Alzheimer’s disease. In the trials, there seemed to be a useful reduction in the unwanted and damaging amyloid protein.
A medicine that could slow or prevent Alzheimer’s disease is prayed for, all over the world. However, giving someone an intravenous infusion twice a month is a costly and time-consuming clinic-based procedure. Any infusion carries a risk that the person will get a temperature, a rash, body aches and other uncomfortable side effects. The experimental infusions, which contain antibodies, have a side effect called ARIA (amyloid-related imaging abnormalities) which can include brain swelling or tiny bleeds in the brain. Lecanemab was reported to have caused fluid to form in the brain in more than 1 in ten of the patients. Worryingly, more than 17% of the people in the trial had small amounts of bleeding in the brain. Yale Medicine in January 2023 announced an estimated cost of $26,500 per year based on information from Esai, the pharmaceutical company.
Other even more expensive medicines have been approved for other conditions, but in general they are for very rare diseases, and dementia is not rare. The cost to the system of dementia is already greater than cancer, heart disease, and stroke put together. It is not clear how much of that existing economic burden would be reduced by introducing expensive dementia medicines, which so far only show mild improvements in patient well-being in the early stages. Even if it was affordable and available at once, there would be many years of a comet’s tail of people who are too late for the new treatment. Currently there is concern about the lack of resource for them. If money’s tight, it’s hard to see how an additional, marginally effective, treatment could be provided for.
Then in the month of May 2023, Eli Lilly reported that it has a medicine that works in the same way as Lecanemab. It’s called Donanemab. Again, it involves IV infusions of antibodies. Apart from the burden of time, money, and side effects from having an infusion, it sadly caused brain swelling in up to a third of patients. Patients have died because of side effects.
These medications, insofar as they make any difference, work in the early stages of the disease. That’s a time when many people affected are either unaware, or in denial, about the symptoms they are experiencing. If the health system is ever going to provide this sort of treatment, it needs to gear up diagnosis and make it earlier, much earlier than at present. That’s not just about more and faster patient pathways, but also wider entry points for worried people in the early stage with mild problems who currently might be sent away for a long time until their problem is significant enough to get medical attention. One reason for sending that person away is that for mild cognitive problems, about a third will get better anyway, another third won’t get worse, and only the last third are going on to get dementia. So there is the potential risk that two thirds of the people with mild cognitive problems get put on potentially risky IV therapy when they weren’t going to get dementia anyway. Or people have to wait till their symptoms are significant by which time they’ve missed that early window when the treatment seems to work best. It’s very difficult.
In addition, new clinics need to be funded and set up to provide hundreds of thousands of IV infusions, or some way found of people having IV infusions themselves at home, as currently happens for some other conditions. As it is only going to happen in the earliest stages, there is some hope that the patient would be able to follow the instructions about how to do this safely. If the troubling symptom that brought them to the doctor in the first place was a reduced capacity to learn new things, it will be tricky.
In the UK now, where there are current concerns about waiting times and availability of NHS services, and austerity measures have reduced local authority social services support, it is hard to see where the revenue would ever come from to pay for new treatments like this. Even the most exaggerated reports do not suggest that all 900,000 people with dementia in the UK would benefit – just those in the earliest stages. But only if they can be found, and if they would or could put up with the burden of regular infusions. But it is still a lot of people.
Research has said that people are more afraid of dementia than cancer, so they might go to extraordinary lengths to get a treatment. Money, time, and discomfort might not be a chilling factor for frightened people who have time and money. But how does that sit with the fact that people seem to ignore what we already know about brain health? We know that avoiding head injury matters, but it has been extraordinarily difficult to persuade those involved in contact sports. We know that exercise matters, but it plays a very small part in many lives. There are relatively inexpensive life style interventions that people are not undertaking.
The most important thing about the drug development story is how it demonstrates that scientists are working tirelessly to look for a treatment or cure, and they need money to do that. Compared with the money poured into cancer research, dementia is a poor relation. The scientists are making progress, but it’s very hard to talk about their progress without creating headlines that torment those who are currently living with dementia. There is no magic solution. That’s very important for us all to remember. And we need to seek solutions for this other problem of explaining early results in a way that is cheerful but doesn’t give false hope to people living with dementia here and now. The cure has not been conjured up. It’s all still a trial.