The first drug shown to slow the destruction of the brain in Alzheimer’s disease will not be available on the NHS after a decision by the medicine’s regulator.
The decision on funding lecanemab has caused upset and disappointment from those hoping the drug could help fight a horrible and devastating disease.
But the decision is also not a shock.
Lecanemab is not a “wonder drug”. The European Medicines Agency looked at the same data as the UK and concluded the drug should not be prescribed to anyone outside of a clinical trial.
But what would it take to get an Alzheimer’s-slowing drug covered by the NHS?
The National Institute of Health and Care Excellence has the job of working out what is a good use of taxpayers’ money. It is where the emotion, desperate need and lobbying for therapies come up against the cold, hard calculations of cost-effectiveness.
Dementia drugs that help manage symptoms, such as confusion, have been approved in the past.
But this is the first time a drug that changes the course of the disease has been assessed. This is a more familiar experience in other diseases. Earlier this summer the cancer drug Enhertu, which can extend the lives of some people with incurable breast cancer, was rejected because it was too expensive.
But even very expensive drugs – I reported on a one-off gene therapy that has an official cost of £2.6m – can be approved if the benefit is big enough.
Lecanemab has issues with its effectiveness, its cost and also its safety.
It was lauded for being the first drug to do something, anything, to slow the course of Alzheimer’s disease. For a field that had faced repeated failure, this was a truly significant moment when the data came out in 2022. But as I wrote at the time, the effect is small.
Lecanemab does not cure, reverse or halt Alzheimer’s disease. It slows the pace of decline.
In trials, the disease continued to rob people of their brain power, but that decline was slowed by around a quarter over the course of the 18 months of treatment. On an 18-point scale, ranging from normal to severe dementia, those getting the drug were 0.45 points better off.
How meaningful those effects are is still hotly debated by researchers.
Some argue they are giving people vital independence for longer. Others contend the effects are so small that a doctor would be unable to tell the difference between a patient getting lecanemab for 18 months and another getting a placebo (pretend treatment). Others say that patients should be allowed to make an informed choice about what is important to them.
The data on the drug came from a large-scale trial involving 1,795 volunteers with early stage Alzheimer’s. But those enrolled were healthier and younger than people when they are normally diagnosed. It raises questions of the drug’s “real-world” effectiveness in older, frailer people with multiple health conditions, and even “mixed” dementia which could be part Alzheimer’s and part another disease.
A more potent drug with a clearer impact on the course of Alzheimer’s disease could swing those cost-effectiveness calculations.
That could potentially still be lecanemab. It is possible that starting treatment even earlier in the disease or continuing treatment for longer would have greater effects. This is still unproven.
Or it could be that lecanemab shows the way and a future drug that follows in its footsteps could deliver the greater benefit. Medical research often needs the initial breakthrough that others can build on. The first HIV drugs eventually paved the way for modern anti-retroviral therapy that gives people a near-normal life expectancy.
Costs are the other side of this equation. A cheaper drug has to do less in order to meet that value-for-money threshold.
Lecanemab is pricey. The drug itself costs about £20,000 per patient per year (based on US prices). But the surrounding care doubles that cost in the NHS (and private fees are likely to be even higher).
It requires an expensive PET (positron emission tomography) scan or a lumbar puncture to sample cerebrospinal fluid to confirm patients actually have Alzheimer’s disease – as there are many types of dementia – before treatment can start.
It then requires an infusion into a vein every two weeks to administer and further expensive brain scans to monitor known side effects.
One option is to negotiate a better price, and with other drugs on the horizon such as donanemab there will be competition that could bring down prices.
There is still time for that to happen. NICE issued its draft decision on Thursday, which will be finalised later in the year.
However, pharmaceutical companies want to recover their years of research and development costs – and the field has produced a lot of expensive duds and dead-ends.
Both lecanemab and donanemab are also a very expensive type of drug called monoclonal antibodies. These are the lab-made versions of the antibodies that your immune system naturally makes to fight disease.
For Alzheimer’s disease they have been designed to target a sticky protein – called amyloid – that gunges up the gaps between brain cells. Amyloid is a key hallmark of Alzheimer’s and the antibodies remove it.
However, these are difficult to design and manufacture, which inevitably makes them expensive drugs. You cannot have monoclonal antibodies at aspirin prices.
The drug is also not allowed in people who have certain genetic mutations that actually increase their risk of Alzheimer’s, so a genetic test is required.
Dangers of these drugs include brain swelling and brain bleeds or haemorrhages, and some have been fatal. So monitoring adds to the costs.
Blood tests for Alzheimer’s, drugs that require fewer infusions or produce less side effects, or better ways of predicting who is at risk of side-effects could all theoretically reduce the cost of care around these drugs too.
But as it stands, to treat the 70,000 people who would technically be eligible for the drug in England could cost about £1.4bn each year and a similar sum in NHS care. That has been evaluated as a poor use of taxpayer’s money for a drug with an impact widely considered “small”.
It is still a historic week. For the first time a drug has been licensed that can slow the pace of Alzheimer’s disease.
For decades dementia was just seen as an inevitable part of ageing, then it became clear this was actually a disease. Now, there is optimism we are on the cusp of being able to do something about it.