Why there’s excitement and skepticism about a new Alzheimer’s drug, lecanemab

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Despite decades of research and billions of dollars of investment, no treatment has been conclusively proven to slow the progression of Alzheimer’s disease.

Two pharmaceutical companies have developed drugs that they say will do just that.

On Tuesday, the full results of a global human trial of the drug, called lecanemab, will be presented at the Alzheimer’s Research Conference in San Francisco.

Biogen in the US and Eisai in Japan have so far only finalized the results of human trials in September. news releasePatients with early-stage Alzheimer’s who received lecanemab over the 18-month period of the study performed 27% better on cognitive tests than those who received placebo.

More than 600,000 Canadians have dementia, with Alzheimer’s disease being the most common form.of Canadian Alzheimer’s Association That number is projected to reach 1 million by 2030.

While some experts say there is a lot of optimism about lecanemab’s potential, others have caution and questions: What will the full data reveal? how much does it cost? How much of Alzheimer’s disease’s devastating effects, including severe memory loss, mood changes, and inability to perform basic tasks, can be reversed.

Broadly speaking, the results suggest that lecanemab slowed progression of early-stage Alzheimer’s disease by 4-5 months over the 18-month study period.

Dr. Sharon Cohen, Medical Director of the Toronto Memory Clinic, one of lecanemab’s clinical trial sites, said:

“This is a very hopeful time for Alzheimer’s disease,” Cohen said in an interview with CBC News. for the first time.”

Cohen will be one of the researchers presenting lecanemab data at the Alzheimer’s Disease Clinical Trials Conference on Tuesday.

“If we can slow the progression of the disease even a little bit, that’s a win, because we know this disease is going to go on and on,” Cohen said. “We couldn’t stop the progress so far.”

“A 27% improvement costs a lot of money.”

A news release from Biogen and Eisai described the finding that the drug slowed cognitive decline by 27% as “highly statistically significant.”

However, some question how important it is for people with early-stage Alzheimer’s disease.

Dr. John Forsyeth, an emeritus professor of neurosurgery at the University of California, San Francisco, who has worked with biotech companies to find a cure for Alzheimer’s disease, is skeptical of lecanemab.

“I don’t think it’s in the health system’s interest to spend a lot of money on a 27% improvement,” Forsayeth said in an interview. “If it had a really huge effect, you can have an argument.”

The price of lecanemab has not been announced, but a similar drug called aducanumab, developed by Biogen and Eisai, hit the market last year at a price of $56,000 a year.

See | Aduhelm Risks and Benefits Discussion:

Much of the concern among experts about new drugs from Biogen and Eisai stems from what happened last year with aducanumab, marketed under the brand name Aduhelm.

U.S. Food and Drug Administration Granted accelerated approval to Aduhelm in June 2021apart from little evidence It actually slowed the progression of Alzheimer’s disease. (Neither Canadian nor European regulators have approved the drug.)

Aduhelm’s US launch fell through because many health insurance companies and hospitals were reluctant to pay for the drug, saying it was not an effective treatment.The final nail was put in the coffin in January when the U.S. Medicare system Rejected To cover it outside of clinical trials.

Biogen and Eisai have also submitted lecanemab for accelerated approval by the FDA, with a decision expected in early January.

Are drug targets the real cause of Alzheimer’s disease?

Lecanemab and aducanumab work similarly. Both are monoclonal antibodies (hence the -mab at the end of their names) and both target a protein called amyloid.

There is widespread scientific consensus that amyloid plays a role in the disease, as the brains of people with Alzheimer’s disease have abnormal clumps of this protein around and between neurons.

but there is There is no consensus on what exactly that role is.

Simply put, the question is whether these amyloid masses are the root cause of Alzheimer’s disease, or just an effect. There is some debate about exactly how it develops.

Hypothesis that amyloid causes Alzheimer’s disease dominate the field It drives the majority of pharmaceutical research. However, until lecanemab, all experimental drugs that successfully inhibited amyloid production failed to slow cognitive decline.

“It’s a complex disease. It requires different treatments, and it’s not all about lowering amyloid,” Cohen said.

Drugs like lecanemab “need to be complemented and augmented by other drugs before we actually have a therapeutic cocktail that really works for this devastating disease,” says University Health in Toronto.・Dr. Donald Weaver, a senior scientist at the Network’s Crenville Brain Institute, said: .

“The brain is the most complex being in the universe, and Alzheimer’s is probably the most complex disease of the brain,” Weaver said in an interview. It’s not what you should do.”

He contrasts treating Alzheimer’s disease with treating hypertension.

“There is no single high blood pressure drug,” Weaver said. “So why would you expect there to be one magic bullet that will cure Alzheimer’s disease? I think that’s naive.”

The search for an Alzheimer’s cure in Weaver’s lab his theory Amyloid is not just a harmful toxin, it functions as part of the brain’s immune system.

In Weaver’s theory, amyloid causes Alzheimer’s disease when its purpose of fighting infection is misdirected. , inadvertently start killing brain cells,” he said.

This makes Weaver aiming to develop drugs that modulate amyloid rather than clear it, like monoclonal antibodies like lecanemab.

“I see it like a thermostat and we’re spinning [amyloid] It’s less hostile to brain cells, so it lowers it,” he said.

In addition to Weaver’s belief that Alzheimer’s is an autoimmune disease, other researchers are looking at links between Alzheimer’s and diabetes, and investigating possible environmental and health risk factors. increase.

7th leading cause of death worldwide

Dr. Saskia Sivananthan, chief scientific officer of the Alzheimer’s Association of Canada, says multiple treatments will no doubt be needed.

“We are not that advanced and should not be affected by this disease,” Sivananthan said. Part of the lack of progress is the small proportion of

Alzheimer’s disease, the seventh leading cause of death worldwide, accounts for less than 1.5% of the global health research output. world health organization.

Still, some people hold out hope for new drugs. Among them is Lorraine Klein, who has 1,795 of his participants worldwide in clinical trials of lecanemab.

Every two weeks beginning in 2020, Klein traveled from his home in Coburg, Ontario, to the Toronto Memory Clinic for 90 minutes to receive an IV.

She doesn’t know yet, but she’s definitely taking lecanemab now that the research phase of the trial is over.

Once the lecanemab IV was in her bloodstream, Klein said, “I’m very happy about it. It may clear the amyloid protein in my brain.

Klein, 73, said she worked as a cashier at a grocery store and found she couldn’t remember the number code for certain vegetables. Cognitive tests and brain scans confirmed her early stage Alzheimer’s disease, making her eligible for lecanemab research.

“It was really scary at first,” Klein said, adding that her biggest fear was forgetting her husband. Hmm.”