New treatment for Alzheimer's disease Approved in the United States In Japan?

"Seven million".

This is the number of dementia patients aged 65 and over as of 2025, the year after next, estimated by the Ministry of Health, Labor and Welfare.

Alzheimer's disease accounts for 60% to 70% of these cases, but there is still no fundamental cure.

Under these circumstances, a new drug called "lecanemab" developed by major Japanese pharmaceutical company "Eisai" and others was approved in the United States on the 6th of this month, and it is expected that it will actually start to be used by patients.

The advent of this drug may change the way dementia is treated.

(Science and Culture Department reporter Hajime Oka)

"I don't want my symptoms to progress any further."

Dementia clinic in Tokyo.

As the number of patients increases due to the aging of society, doctors who have been examining patients for many years feel that the reduced interaction between people due to the corona crisis is affecting the worsening of symptoms.

Memory Clinic Ochanomizu Takashi Asada

"I think there are more than a few people whose cognitive functions are declining because of the negative effects of the coronavirus pandemic. The medicines that are currently available are not enough to provide sufficient therapeutic effects, so I encourage them to exercise and have opportunities to interact with others." I am actively trying to get them to make it.”

The clinic recommends regular exercise.

I hope that the stimulation of muscle training that can be easily done will slow down the progression of the symptoms as much as possible.

I want to stay healthy for as long as possible.

This is the wish of many elderly people.

Man in his 60s

: "I'm doing everything I can with the feeling that I won't lose to dementia."

Woman in her 60s : "I tend to forget things,

so I don't want my symptoms to progress any further."

Alzheimer's disease effect of new drug

Alzheimer's disease accounts for more than half of all dementias.

Since the German physician Alois Alzheimer first described it more than 100 years ago, research into its causes and treatments has progressed around the world.

However, the detailed mechanism is still not fully elucidated.

Currently, there are four types of Alzheimer's disease drugs approved in Japan.

By enhancing the function of the remaining nerve cells, the progress of the symptoms is delayed for several years, but the destruction of the nerve cells in the brain itself cannot be stopped.

For this reason, research institutes and pharmaceutical companies around the world have been working to develop fundamental therapeutic drugs that can suppress the progression of Alzheimer's disease itself.

One of its targets has been the abnormal protein "amyloid β" that accumulates in the brain.

Amyloid β is known to accumulate in the brains of patients with Alzheimer's disease.

It is believed that this "amyloid β" damages the nerve cells in the brain, leading to a decline in cognitive function.

Nerve cells that have been damaged cannot be restored.

However, if the progression can be slowed before cognitive decline becomes incapacitating, the patient's quality of life can be greatly improved.

It is expected to lead to a longer period of time before nursing care is required and more time spent with family members, and will be a major advance in terms of both dementia treatment and social significance.

“Lecanemab” developed by “Eisai” and others is also an antibody drug designed to remove “amyloid β”.

It is a mechanism that binds an artificially synthesized antibody to "amyloid β" so that immune cells can decompose it.

Last November, the results of a final-stage clinical trial presented at an international conference on dementia showed that patients who received lecanemab improved their health after one and a half years compared to those who received a placebo. The decline in cognitive function was suppressed by about 27%, showing the effect of slowing the progression of symptoms itself.

Drugs that remove "amyloid β" have been developed so far, but sufficient data could not be shown to suppress the decline of cognitive function.

For this reason, the clinical trial results of lecanemab, which clearly showed its efficacy, were taken by experts with surprise.

Professor Takeshi Iwatsubo , The University of Tokyo

“We were able to demonstrate scientifically groundbreaking results in response to hypotheses that many researchers had challenged over the years. I believe that this drug will be a breakthrough in future dementia treatment development.”

And on the 6th of this month, "lecanemab" was approved as a therapeutic drug by the FDA = US Food and Drug Administration.

The reason for the approval is that it showed the effect of reducing the abnormal protein "amyloid β" in the brain of the patient.

This approval was made under a mechanism called "accelerated approval" to provide treatment to patients with serious diseases earlier, and was evaluated based on the results of intermediate-stage clinical trials.

The FDA plans to conduct additional analyzes of the results of late-stage trials to reassess its efficacy.

"Possibility of approaching the target"

Why was lecanemab able to suppress the deterioration of cognitive function?

Professor Kenjiro Ono of Kanazawa University (Department of Neurology) believes that the secret lies in targeting a specific stage of "amyloid β".

In an effort to find out the cause of Alzheimer's disease, I have been observing "amyloid β" for many years using a special device called a high-speed atomic force microscope.

"Amyloid β" accumulates in the brain as fibrous masses as individual grain-like particles gradually gather over a period of more than 10 years.

In fact, many of the drugs that have been developed so far were designed to remove fibrous masses of "amyloid β."

However, "lecanemab" is designed to bind at a stage called "protofibril" before it becomes fibrous.

Professor Ono had long suspected that this stage, called protofibrils, had an adverse effect on neurons in the brain.

So he filmed how lecanemab works on protofibrils.

This time, the video released for the first time captures how "lecanemab" binds to "amyloid β" before it becomes a fibrous mass.

"Lecanemab" surrounds "amyloid β" and prevents it from becoming fibrous.

Then, using the bound "lecanemab" as a mark, immune cells remove "amyloid β".

Professor Kenjiro Ono, Department of Neurology, Kanazawa University

"The fact that the antibody that binds to the 'protofibril' stage before it becomes a fibrous mass is more effective means that this stage is the worst among 'amyloid β'. We believe that the results of lecanemab this time may greatly change future dementia treatment."

Risk of brain swelling and bleeding

While expectations are high for lecanemab, clinical trials to date have pointed out that the risk of brain swelling and bleeding increases.

Two of the patients who continued to take the drug after the trial ended were reported to have died of cerebral hemorrhage.

Regarding this, "Eisai" explained in November last year that "the death was not due to" lecanemab "because the two originally had serious complications."

In addition, there was no difference in the percentage of people who died during the clinical trial period with or without administration.

In the future, it will be necessary to carefully verify what kind of people are at increased risk.

When will it reach Japanese patients?

Challenges

When will lecanemab reach Alzheimer's disease patients in Japan?

After receiving approval in the United States, Haruo Naito, CEO of Eisai, held a press conference on January 7, stating that he would like to apply for approval in Japan as soon as possible, and indicated his intention to aim for approval within this year. I'm here.

However, even if approved, the drug is not available to all patients.

The target is limited to patients with early Alzheimer's disease who have relatively mild symptoms and who have been confirmed to have accumulated "amyloid β" in the brain.

There are many diseases other than Alzheimer's disease that cause dementia, and it is not easy to accurately find out whether it is Alzheimer's disease or something else, especially in the early stages.

The key to using this drug effectively is how early we can detect patients with early Alzheimer's disease.

For this reason, it has been pointed out that there is a need to create a system for testing and diagnosis.

For the diagnosis of Alzheimer's disease, a device called PET (pet), which can take images of tissues inside the body, is widely used.

Using PET, it is possible to visualize how much "amyloid β" has accumulated in the brain.

In this PET image of the brain, areas where "amyloid β" accumulates are colored red and yellow.

However, PET equipment is large and expensive, so the cost of examination is high, and the medical institutions where it is installed are concentrated in urban areas.

Furthermore, it is not easy to secure specialized facilities and technicians because a special drug that emits weak radiation is administered during imaging.

On the other hand, tests using cerebrospinal fluid are also sometimes used, but because the sample is collected by inserting a needle into the waist, the burden on the patient's body is heavy, and it is a problem as a method to find the target patient from many people. is said to be

Experts say that it is necessary to prepare a diagnostic system in preparation for the emergence of new therapeutic agents.

Kenji Ishii, Research Director, Research Institute, Tokyo Metropolitan Geriatrics and Gerontology Center

"In some rural areas, there is only one hospital in a fairly large area that can perform PET examinations. Rather than finding them, I think we need to narrow down the people who really need them and have them take PET scans.”

Required blood diagnostic technology

Therefore, what is expected is the emergence of diagnostic technology that is simpler and less burdensome for patients.

Shimadzu Corporation, a major analytical equipment manufacturer in Kyoto, is working on the development of a device that can more easily diagnose Alzheimer's disease by applying the research of Koichi Tanaka, who won the Nobel Prize in Chemistry.

Only a few drops of blood are used for the test.

By separating the proteins necessary for analysis from the blood and comparing their weights, we can estimate how much "amyloid β" has accumulated in the brain.

We have scientifically verified that the test accuracy is close to 90%, which is close to PET performance, and published it in a global academic journal.

Furthermore, from January, we will start research in Oita Prefecture in collaboration with local universities and medical associations to see if this device can be used for early diagnosis on actual patients.

Tsukasa Takeuchi, Group Manager, Analytical & Measuring Instruments Division, Shimadzu Corporation,

"By establishing a method for detecting signs of Alzheimer's disease by collecting blood that is less burdensome on the body, we can find people who can be expected to benefit from drugs. will benefit from the drugs that will emerge in the future, leading to earlier treatment.”

Is it possible to judge risk just by daily conversation?

Research is also underway to use AI to lead to early diagnosis.

A company in Tokyo that develops artificial intelligence is conducting research to detect signs of dementia from everyday conversations.

AI analyzes daily conversations of about 5 to 10 minutes and detects the characteristics of dementia patients, such as ▽ many reference words and ▽ lack of concreteness, and how far the symptoms have progressed. determine risk.

He has also published a paper summarizing the results of verification that the accuracy of predicting dementia from a conversation of about 5 minutes is 90%. is assumed to have an accuracy close to

We hope that this technology will be used as a supplementary aid in interviews with primary care physicians, etc., and in cases where the risk is high, it will lead to diagnosis by specialists.

Executive Officer Hiroyoshi Toyoshiba, FRONTEO

“Daily conversations can be analyzed very easily. As new treatments are being developed, we need to find patients early and have them receive proper treatment. I believe that I can contribute to

Will dementia treatment enter a new era?

Regarding drugs to treat Alzheimer's disease, major overseas pharmaceutical companies are also developing new drugs that remove "amyloid β", and the results of final-stage clinical trials are expected to be revealed this year.

A number of companies are entering the development of equipment and technology that will lead to early diagnosis, and the movement toward the spread of new drugs is accelerating.

Then, if "lecanemab" becomes available, isn't the price a concern?

"Eisai" has set the average price of the drug in the US at $26,500 per person per year, or about 3.5 million yen (if the drug is administered once every two weeks for a year).

The price has not been announced yet in Japan, but if it is approved, it is expected to be somewhat expensive.

There are also concerns that if public medical insurance covers this, it will strain the insurance finances.

Furthermore, it is necessary to deepen the discussion not only from the standpoint of patients and their families, but also from the perspective of medical economics, as to whether the effect of delaying the decline in cognitive function shown in clinical trials is worth the price. pointed out by several experts.

"Lecanemab" is a "drug that slows down the progression of Alzheimer's disease" and is not a drug that completely cures Alzheimer's disease and restores nerve cells.

Excessive expectations should be avoided, but it can be said that it has the potential to greatly change the way we face Alzheimer's disease, along with the technology to find patients at an early stage.