This is the experimental drug that promises to stop Alzheimer's

The neurologist Juan Fortea, from the Sant Pau hospital (Barcelona), who has participated in the lecanemab trial. Massimiliano Minocri

For a few days now, the neurologist Juan Fortea has had more and more patients asking him for “this new drug against Alzheimer's”.

The doctor works at the Sant Pau hospital in Barcelona, ​​one of the 12 Spanish centers that have participated in a large international clinical trial with the experimental drug lecanemab.

The results, still preliminary, suggest that it reduces cognitive decline by 27% in people with early Alzheimer's, according to Eisai and Biogen, the two companies that have developed it.

This announcement has been made by press release and without any type of review by independent experts.

The two companies have skyrocketed on the stock market, but for now it is not known if lecanemab really has any benefit for patients.

Fortea does not hide his impotence.

This is the first molecule in 20 years that appears to have some effect—albeit a slight one—against the progression of the disease.

But the lack of data and the drug's approval process, which will take about two years at best if it finally proves effective, mean that we have to wait.

"I couldn't be more excited, but I can only ask for caution," highlights the doctor, who collaborates with the two pharmaceutical companies and is a spokesperson for the Spanish Society of Neurology (SEN).

Alzheimer's is often spoken of as a family disease, because it not only affects patients —1.2 million in Spain— but also their loved ones and caregivers on whom they totally depend —together they number more than five million—.

So far, the search for a cure has been fruitless.

The only approved drugs mitigate some symptoms, but they do not stop the progress of this disease that affects 50 million people around the world and will increase its incidence in the coming decades.

1,795 patients from 14 countries have participated in the lecanemab clinical trial.

All had symptoms of mild Alzheimer's, and their brains had a buildup of amyloid beta proteins, a hallmark of the disease.

At this stage, patients begin to have recent memory failures, but remain independent to go out, cook and lead a normal life.

After 18 months of the trial, the cognitive decline of those who took the drug was 0.45 points lower on a scale of zero to 18 points than those who took placebo, according to the two companies.

The key is whether that statistically observed improvement translates into a real clinical benefit, for example, that a person with Alzheimer's can remain independent and not have to enter a nursing home.

That 27% means winning days, months, years to dementia?

It is impossible to know with the data that the companies have published.

The two pharmaceutical companies have said in a statement that they expect to reveal more details by the end of November and publish all the results in a journal, with the review of independent experts, an essential guarantee for quality science.

But with these data on lecanemab they are already going to apply for approval in the US as well as in Japan and Europe, where they hope to do so before March 2023.

The scale used in the study is based on the subjective perception of patients and caregivers about their mental capacities, a common standard in the diagnosis of the disease.

"With these data it will be very difficult for a patient or a caregiver to notice the improvement," says David Pérez, head of neurology at Hospital 12 de Octubre in Madrid, who has not participated in the trial.

“The benefits of lecanemab are less than those of donepezil, one of the current drugs, which reduces cognitive impairment by 0.53 points.

Generally, for there to be a real improvement, a change of 2.5 points must be achieved,” adds the doctor, who is also a member of the SEN.

The drug has caused side effects such as brain hemorrhages in 17% of patients (vs. 8.7% in the placebo group).

In addition, it is administered intravenously every 15 days.

Giving it to all Spaniards with mild Alzheimer's would present an unaffordable challenge for the health system, according to several doctors consulted.

Eisai and Biogen are already exploring the possibility of giving this drug subcutaneously.

A day after the announcement, the two pharmaceutical companies had spectacular gains on the stock market.

US-based Biogen fluffed out almost $10 billion (a similar amount in euros), which almost covered its losses for this entire year, Reuters reports.

Precisely Biogen was the promoter of aducanumab, a drug against Alzheimer's approved by the US drug agency (FDA) despite the fact that many experts warned that it does not work.

The medicine, which costs 40,000 euros, has been an economic and medical failure.

“Economic gains, not scientific”

Jesús Ávila, a veteran Alzheimer's researcher, is highly critical of the ad.

“It is the same story that we have seen on other occasions.

Companies make economic gains, but not scientific or medical ones”, he highlights.

Eva Carro, principal investigator of the Network Biomedical Research Center on Neurodegenerative Diseases, is also blunt: “I hope that neither the FDA nor the European Medicines Agency approve this drug, or even consider it, until all the data are published and reviewed. by independent experts.

In 1906, a 50-year-old woman suffering from paranoia, insomnia, sudden mood swings, memory loss, and confusion became the first case of a new disease described by German neurologist Alois Alzheimer.

The patient's brain was riddled with protein fibrils and plaques.

It's the same mark seen in most people with Alzheimer's.

It is now known that deposits of harmful molecules begin to appear about 20 years before the first symptoms.

By the time the disease is diagnosed, it is already too late to prevent it.

And 116 years after its discovery, its causes remain unknown.

The amyloid beta protein theory has been one of the most researched.

It is not yet clear if it causes Alzheimer's or is just a side effect.

There are many other possibilities—buildup of tau (another protein), an autoimmune process of inflammation, viral infections.

In 1992, the Swedish Lars Lannfelt and the American Dennis Selkoe discovered "the Swedish mutation", a genetic defect in a single family in Sweden that predisposed them to accumulate plaques of amyloid protein in the brain and to suffer from Alzheimer's.

In 2003, Lannfelt, a researcher at the Karolinska Institute, co-founded the company BioArctic to develop a molecule capable of cleaning these plaques from the brain and trying to cure the disease.

That molecule is lecanemab, a monoclonal antibody inspired by immune system proteins that reduces amyloid beta and that BioArctic has developed in collaboration with the Japanese Eisai.

This company in turn collaborated with Biogen in the development of the unsuccessful aducanumab.

Last year, after obtaining promising results, the US FDA began the rapid evaluation process for lecanemab.

A researcher, in the brain bank of the CIEN Foundation. Inma Flores (EL PAIS)

The results of lecanemab revive the causal theory of beta amyloid, says Carlos Dotti, a doctor and Alzheimer's researcher at the Severo Ochoa Molecular Biology Center (CSIC).

"It is possible that the original event of the disease is amyloid beta," says Dotti.

“But cleaning it out of the brain does not cure the disease.

In addition, there are people with beta amyloid who reach the age of 90 or more without a trace of Alzheimer's, ”he highlights.

Miguel Medina, deputy scientific director of the Network Biomedical Research Center on Neurodegenerative Diseases, believes that lecanemab will mark a "milestone" in research if the announced results are confirmed.

However, the effect for patients will be “very modest”.

“This drug has better prospects than the previous ones, but until it is approved by the FDA and then by the European Medicines Agency, we will not know what its indications will be and for which patients.

Can only people with early Alzheimer's take it or others with pre-Alzheimer's as well?

In any case, this is not a cure.

It is only a first door that opens towards more effective future treatments”, he highlights.

Miguel Baquero is a neurologist at Hospital La Fe in Valencia.

Twenty of his patients have participated in the lecanemab trial.

“Does this medicine work?

You really don't know, because the variability of the initial stages doesn't allow us to be sure”, he acknowledges.

“We need to follow these patients longer.

For this reason, when they ask me about these drugs in the consultation, I say that for the patients of the present we have the drugs of the present and that these are the medicines of the future, for the patients of the future.

In this decade there may be an important change thanks to early diagnosis and the use of this type of drug.

It is probable, but not certain”, he predicts.

Results from clinical trials with gantenerumab, another monoclonal antibody developed by Roche, are expected before the end of the year, and in mid-2023 Lilly plans to reveal the results of its trial with donanemab, another monoclonal antibody.

This class of drugs, already approved for other uses, such as cancer, are among the most expensive in the world.

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