Debate about the Alzheimer's medication Lecanemab, because UK approval is limited

debate about the Alzheimer drug Lecanemab-one of the first medication that slows down cognitive dismantling in humans-is intensifying among researchers and clinics about whether the potential advantages of treatment outweigh the risks.

On August 22nd, the British drug authority Medicines and Healthcare Products Regulatory Agency gave the green light for the medication. At the same time, however, the British Health regulator Nice, who determines whether medication is offered in the state -funded British health service (NHS), said in a draft that Lecanemab is not made available on the NHS, since the advantages are too low to justify the high costs.

"The unusually long time you spent with the examination of the drug suggests that this was not a easy or easy decision," said psychiatrist Robert Howard from the University of College London in an explanation to the Science Media Center in Great Britain.

US regulatory authorities were the first to have the medication in 2023, and the European Medicines Agency (EMA) now checks their decision after an appeal from the pharmaceutical manufacturer.

amyloid target

The decision of the EMA also met with mixed reactions at the Alzheimer community. "The emotions are really high here," says biochemist Christian Haass from the Ludwig Maximilians University in Munich, Germany, who does not agree to the decision. "It is the first disease -modifying medication that we have had for more than 30 years." According to Haass, the refusal of patients to access Lecanemab means that many lose the opportunity to win valuable time.

lecanemab or leqembi is a monoclonal antibody, the amyloid, a substance that is eliminated in the brains of people with Alzheimer's into toxic lumps. The drug, manufactured by Eisai in Tokyo and Biogen in Cambridge, Massachusetts, is also approved in China, Japan, South Korea and the United Arab Emirates.

Others welcome the EMA and say that the drug effectively reduces the amyloid values ​​in the brain, whether the resulting reduction in cognitive degradation will lead to clinically relevant advantages for the patient remains unclear. They state that the possibility of serious complications such as bleeding or swelling in the brain caused by a side effect called amyloid -related imaging effects (ARIA), although low, is a great concern. "A reasonable assessment of the risks compared to the advantages of this drug should make people be very skeptical," says Matthew Schrag, neurologist at Vanderbilt University in Nashville, Tennessee.

modest effects

whether lecanemab, which is administered by infusion, offers humans a clinically sensible reduction in cognitive degradation, has long been discussed.

A clinical phase III study of the drug, which was published in 2022, comprised 1,795 people in the early stages of Alzheimer's disease and showed that those who received the medication showed a 27% reduction in cognitive degradation compared to those who received a placebo after 18 months. Some researchers celebrated the news as a win for the field. However, others argued that the effects are too low to have a significant effect on the patients.

One of the reasons for this difference in perspective is how people look at the data, says Sebastian Walsh, a public health researcher at the University of Cambridge, Great Britain. The 27% reduction represents the relative difference in the amount of cognitive degradation that the group has experienced with the medication compared to the placebo group. However, the absolute difference in cognitive function is much lower: 0.45 points on an 18-point scale. "People can extract what they want from the effect size," says Walsh. "If you want to sell the medication, you could concentrate on relative changes - and if you are very skeptical, you could talk about the absolute differences."

But even small effects can become significant over time, especially in the later stages of the disease when the breakdown progresses faster, says Walsh. "Ultimately, it depends on what you think, what long -term effect will occur, and we have no answer."

Now there are some long -term data. At the Alzheimer Association International Conference (AAIC) in Philadelphia last month, Eisai and biogen presented results from an open extension study that continued to monitor the patients who had received Lecanemab after the phase III study. After three years of continuous treatment, more than half of the patients showed an improvement, and most cases of Aria occurred in the first six months of treatment. They also reported that the rate of cognitive mining returned to placebo level when people dropped the medication, even if the amyloid plaques had been removed before the treatment was ended.

Some are optimistic about these results - Haass says that it is exciting to see that the medication not only eliminates amyloid, but also slows down the spread of Tau, another protein that accumulates in the brains of people with Alzheimer's. Others are more careful. Paresh Malhotra, neurologist at Imperial College London, indicates that the positive results presented on the AAIC were not compared with a placebo so that more data is required to determine the long -term effectiveness of the drug.

The costs are also concerned. Walsh says that in view of the modest effects of the drug, it is difficult to justify the costs for the administration of the drug (which costs more than $ 20,000 per year in the United States) and to justify the necessary procedures such as imaging and genetic tests to identify authorized persons that should be preserved.

security concerns

The greatest concern at Lecanemab is Aria, against which the US Food and Medicines Authority (FDA) has warned in its approval. Although most cases are asymptomatic-and no reported during the initial 18-month clinical study-there were some Aria-related deaths in the extended phase of the study.

Some experts say that although the risk is heavy Aria is low, it is also important to take into account that the drug is administered by Alzheimer's earliest stages. "This is the period in which people have to lose the most," says Schrag. "In this time window, we often encourage patients to travel, think about their wish list and to do the things they want to achieve in life."

Ellis van Etten, neurologist at Leiden University Medical Center in the Netherlands, says that there are still many open questions about Aria and how doctors should react when you see that patients develop these abnormalities during treatment. For example: who will develop serious or life -threatening ARIA? When does Aria become harmless to harmless and when should treatment with Lecanemab be canceled?

Many of the same questions and risks also apply to another amyloid -resistant antibody, Donanemab -made by Eli Lilly in Indianapolis, Indiana -that was approved by the FDA in July. Donanemab seems to offer an approximately equal reduction in cognitive breakdown like Lecanamab-and it was associated with Aria-related deaths.

"We know from biomarker -related work that these antibodies remove amyloid, so we know that they address a fundamental mechanism of the disease," says Malhotra. But these drugs alone will probably not be enough, and it will be important to deal with other aspects of the disease. "It is very likely that we will talk about combination therapies in ten years and that amyloid removal will be part of this approach."