Home Top Global NewsHealthcare It’s just a first step, but this new Alzheimer’s drug could be a huge breakthrough | Jonathan Schott

It’s just a first step, but this new Alzheimer’s drug could be a huge breakthrough | Jonathan Schott

by Ozva Admin
It’s just a first step, but this new Alzheimer’s drug could be a huge breakthrough | Jonathan Schott

meIt’s been 20 years since the last Alzheimer’s drug was licensed in the UK. Since then, great strides have been made in our understanding of the causes of disease. Better diagnostic tests are available, and we may now be on the cusp of new treatments that could have an impact on some of the fundamental brain changes thought to lead to dementia. This morning, the results of a long-awaited trial of a promising new drug, lecanemab, were published in the New England Journal of Medicine. It could have beneficial effects for Alzheimer’s patients, although there are some caveats.

Dementia is defined as a progressive, acquired cognitive decline that interferes with a person’s normal activities. In the UK, it affects more than 900,000 people and is the leading cause of death. Alzheimer’s Research UK estimates that the cost of caring for people with dementia exceeds £25 billion a year. As the population ages, those numbers will increase. In the UK alone, estimates suggest that approximately 1.6 million people will be affected by dementia in 2050.

Just as there are many causes of cancer, there are also many causes of dementia: Alzheimer’s is the most common, accounting for about two-thirds of cases. The disease is particularly associated with the abnormal accumulation of two proteins in the brain: beta-amyloid, which is deposited outside nerve cells; and tau entanglements, which accumulate within them. Most experts believe that the buildup of beta-amyloid triggers a process that includes inflammation and tau buildup, leading to brain cell death and disturbances in brain chemistry. Ultimately, this causes symptoms: Typically, people experience a progressive decline in their everyday memory, followed by loss of their other cognitive functions. This leads to dependency and eventually, and inevitably, death, on average six to seven years after diagnosis.

Today, beta-amyloid can be detected through PET brain scans, cerebrospinal fluid exams, or blood tests (although the latter are not yet commonly used). Accumulation of this protein begins perhaps 20 years before symptoms appear, and about 20% of healthy, asymptomatic 70-year-olds have significant deposition of beta-amyloid in the brain. While this has led some scientists to question the toxicity of beta-amyloid, others see this long pre-symptomatic period as an opportunity, a time when intervention could prevent the onset of cognitive decline.

The central role that scientists believe beta-amyloid plays in Alzheimer’s has made it a key target for drug development. Already in 1999, a paper in the journal Nature reported that vaccination could remove beta-amyloid from the brains of mice. Since then, similar approaches have been tested in humans. Until recently, these attempts were dogged by dismal failures. Multiple drugs failed to show clinical effects and were variably complicated by side effects, such as inflammation and cerebral hemorrhage. One drug, aducanumab, was controversial licensed in the USA last year on the basis of its beta-amyloid-lowering abilities, although questions remain as to whether the drug affects cognitive abilities, and so far it has not been licensed in Europe.

When given to patients with early Alzheimer’s disease, lecanemab not only cleared beta-amyloid from the patients’ brains, but also reduced cognitive decline by approximately 27% over 18 months. Although the duration of the trial was too short to know for sure, changes in other disease markers suggest that beta-amyloid clearance may also be associated with slowing down other disease processes. The drug’s maker, Eisai, will soon apply for regulatory approvals in the US and Europe, with decisions expected before the end of next year. Hot on its heels, definitive trials of another similar drug, Eli Lilly’s donanemab, are expected in 2023.

It is a remarkable achievement that we now have drugs that impact key underlying biological processes and produce at least some beneficial effects on cognition. At a minimum it establishes that Alzheimer’s is potentially treatable, and perhaps one day even preventable, if we could identify and treat the people who might benefit before symptoms begin. But there are important caveats. First, the effects of lecanemab on cognition appear to be modest, and there is already debate as to whether these effects will be of significant benefit to patients.

Longer-term follow-up is vital; if the drug actually slows the disease process, its benefits may become clearer over time. Second, as with any therapy, the benefits must be weighed against the risks. Some mild asymptomatic changes were seen on MRIs in almost a quarter of patients treated with lecanemab. Although excess deaths among those on treatment were not reported, some concerns have been raised about problems that could arise when lecanemab is used in combination with anticoagulants or anticoagulant treatments.

Neither the NHS nor most other healthcare systems are ready to deliver these drugs. While some specialist centers have the required capabilities, the NHS in general simply does not have the infrastructure or staff to diagnose potentially eligible patients. (PET scans that can detect beta-amyloid are not routinely available on the NHS.) Many clinics also do not have the capacity to administer the drug, which is infused every two weeks, or to perform and read multiple security MRIs. Then there’s the cost: Even if a drug were to be authorized, it’s not certain that it would meet the stringent cost-effectiveness assessment required by law. National Institute for Excellence in Health and Care (Nice).

However, we have been down this path before. Stroke services, once fragmented and disorganized, were radically transformed to provide emergency services. “clot busting” therapies when its benefits became apparent. Cancer patients are already diagnosed and monitored using PET scans. And numerous immunotherapies, many of which require intensive monitoring for potentially dangerous side effects, are used on the NHS.

If lecanemab is licensed in the UK, and even if it is initially only available to a small number of patients, it will still be a breakthrough. Funding for dementia research still lags far behind cancer and cardiovascular disease. Further investment will be vital, as no single drug will be a magic bullet. As with cancer, HIV, and heart disease, multiple different treatment approaches are likely to be required. While scientists continue to debate the role of beta-amyloid, there are many other potential avenues to explore: Of the more than 140 drugs in more than 170 ongoing Alzheimer’s trials around the world, three-quarters are directed at other aspects of the disease.

The pressures on the National Health Service they are already huge, but we must prepare for a time when, not if, new treatments are available. We need to provide better care for our patients now and prepare to offer them new therapies in the future. This is a huge challenge, and with an Alzheimer’s epidemic looming, it’s one we can’t ignore.

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