A New Wave of Drugs for Alzheimer’s Disease?
Written by Dr Katherine Paramore
Consultant and Clinical Lead in Old Age Psychiatry
Use of NEW drugs to treat Alzheimer’s disease
Lecanemab and Donanemab are two new drugs in the same family, being trialled for treating Alzheimer’s disease, but in recent weeks there have been starkly opposing reports about them. At the end of April newspapers suggested Lecanemab “could be too risky to take”.
“In Alzheimer’s disease one of the problems is a protein called amyloid, thought to build up and cause damage to brain cells, leading to the symptoms of dementia.”
Within days, following the release of trial results for Donanemab, headlines hailed “the beginning of the end” for Alzheimer’s disease. A third in the same family, Aducanumab, was approved in June 2021 for use in the US but its approval across Europe and the UK is on indefinite hold due to concerns about its efficacy and risk. What are we to make of all this?
For more than 20 years, only four drugs have been licensed for use in Alzheimer’s disease, the commonest cause of dementia in the UK. These drugs help with relieving symptoms rather than treating the disease itself, so do not prevent the disease progressing.
The “holy grail” is to find a treatment that alters (or better still, halts) the underlying disease process, in a way that is both safe and manageable for the people who need to take it. The suggestion is these new drugs may be the first major step in this direction. So what do we know about them?
All three are in a group of drugs called monoclonal antibody therapies. Monoclonal antibody treatments are not new. They have been used for some time to treat various illnesses, including a range of cancers. They work by causing the body’s own immune system to target and destroy abnormal proteins or cells involved with the disease.
In Alzheimer’s disease one of the problems is a protein called amyloid, thought to build up and cause damage to brain cells, leading to the symptoms of dementia. The new drugs are designed to be used in the early stages of the condition, before the damage caused by the amyloid protein build up has become too bad, aiming to prevent further deterioration.
Trial data for Lacanemab
The trial data for Lecanemab, and information released so far about Donanemab (the full study is due to be published later in the summer) suggests that giving these drugs in the early stages of Alzheimer’s disease slows cognitive decline by around 30% over 18 months. More importantly for many facing the condition, the studies also suggest there is a slowing in the decline of skills involved in day to day functioning.
However, these treatments are not as straight forwards as taking a daily pill or patch. They are given as intravenous infusions (by a drip), which would mean people attending hospital every two weeks for Lecanemab and every four weeks for Donanemab, potentially for many months. The trials have taken place over 18 months, but it is suggested treatment could go on in a more open ended way, until it is no longer providing benefit.
Only those with mild symptoms and proven Alzheimer’s amyloid proteins are likely to be eligible. Identifying the latter involves either a lumbar puncture, (a needle is used to draw fluid from the spinal column for examination), or a specialist brain scan.
Potential side effects from treatments
Finally, there are potential side effects from these treatments. The most concerning of these, brain swelling and brain bleeds, are not symptomatic in most who experience them. However a small but significant proportion of people may experience serious symptoms. In the trials of both Lecanemab and Donanemab there have been 2-3 deaths among the 1,750 – 1,800 participants of each study. If these drugs are approved, it is likely some form of monitoring for these effects will be required. In the studies, patients had regular (e.g. 3 monthly) MRI scans and something similar may be required.
If these drugs are approved in the UK, it is likely to mean an overhaul of existing dementia services, which may have ripple effects across other areas of health care. For example, there may be increased pressures on X rays departments, with a new demand for MRI and specialist scans. Approval, if it comes, may be as soon as 2025 leaving time frames tight for services to prepare.
Still An emerging picture
It’s still very much an emerging picture; this first wave of new drugs still face significant hurdles to be approved for use in the UK. Even then, they will only be available for a small proportion of those with dementia, and pose significant challenges and concerns. That said they may have the potential to provide a level of long-term benefit, so we should be excited. We are delighted to see this level of focus in developing new medications for dementia, and the first signs of real progress in treatment, and perhaps even prevention, of Alzheimer’s disease.
