Tuesday 10th September 2024
Debate rages over new Alzheimer’s drugs
Louise Morse
September is World Alzheimer’s Month, and it would have been great if the headline, ‘Drug Hailed by Experts As the Beginning of the End for Alzheimer’s’ describing the new monoclonal antibody drug, lecanemab, had been based on certainty. Instead, a debate is raging in the scientific community over its effectiveness and whether its high costs and the risks of harm are worth its modest results. The European Medical Agency has declined to licence it, and it has also been rejected by Britain’s licensing authority, the National Institute for Health and Care Excellence (NICE). Alzheimer’s disease costs the NHS and Social Services £millions each year. So, what’s being weighed in the balance? If this is not the breakthrough, is there hope for the future?
Clinical trials of lecanemab (marketed as Leqembi) showed that it removed the protein deposits on the brain that are said to be the cause of Alzheimer’s disease but did not improve cognition (the person’s ability to think and reason). It slowed the progress of the disease by up to five months. Usually the figures given quote 27 percent, but Cambridge University researcher Sebastian Walsh says it depends on how the data is presented.
The 27 percent reduction represents the relative difference in the amount of cognitive decline experienced in the drug group versus the placebo group. The absolute difference in cognitive function is much smaller: 0.45 points on an 18-point scale. “People can extract from the effect size what they want,” says Walsh. “If they want to sell the drug, you could stick to the relative changes — and if you’re very sceptical, you could talk about the absolute differences.” 0.45 points on an 18-point scale is so small that some experts say the patients’ doctors won’t see any difference.
Balanced against this tiny result is the huge risk of severe side effects. 20 percent of trial participants experienced brain swelling and bleeds, and there were some deaths.
There is also the price which is generated not so much by the cost of producing the drugs but what the market can bear. The companies in question know that thousands and thousands of people are desperate for a cure. The cost is $26,000 for the drug alone, without the secondary profile of regular infusions, medical supervision and brain scans.
Dr Samantha Roberts, chief executive of NICE said, “This is a new and emerging field of medicine which will no doubt develop rapidly. However, the reality is that the benefits this first treatment provides are just too small to justify the significant cost to the NHS. It is an intensive treatment to give to patients involving a hospital visit every two weeks with skilled staff needed to monitor them for signs of serious side effects, plus the cost of purchasing the drug.
“Our independent committee has rigorously evaluated the available evidence, including the benefit for carers but NICE must only recommend treatments that offer good value to the taxpayer.”
Cambridge University’s Professor Carol Brayne notes the financial burden this will place on the NHS. “The resource requirements for rolling out such treatments are likely to be considerable. Even if approved for only a small proportion of Alzheimer’s patients, a much broader group of people will need to be assessed for eligibility, requiring rapid specialist clinical assessment and tests. The authors question whether this is the best use of these resources, given the strain health systems are already under.”
It can be bought privately in the UK thanks to its approval by the Medicines and Healthcare Products Regulatory Agency (MHRA) which, as some commentators point out, receives 84 percent of its operating budget from pharmaceutical companies.
The American Medicare organisation that funds healthcare for older people is keeping an eye on outcomes by only funding Leqembi treatment with physicians who join and contribute to its information registry.
The big question for individuals is whether the small result justifies the risk – whether to commit to routine infusions of a drug that could cause your brain to swell and bleed, and possibly risk death, in order to delay decline by five to six months.
There is good news, though. A recent study has shown that mild cognitive impairment and early stage dementia were reversed by strict adherence to five life-style ‘interventions’ for 20 weeks. These included diet with added supplements, stress management, exercise and group support.
There are also studies taking place on other aspects of the disease, such as overstimulation of the brain’s immune system, inflammation, and impaired clearing of waste cells. The NHS has said a dedicated team was looking at 27 other Alzheimer's drugs currently in advanced trials that could be approved in the coming years.
And more is being discovered about the brain and dementia. The Lancet recently published a big study showing that 40 percent of dementia cases are avoidable with do-able life style changes. Prevention is always better than cure.
