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Despite decades of research and billions of dollars, no treatment has ever definitively proven to slow the progression of Alzheimer’s disease.
Two pharmaceutical companies have developed a drug that they say does just that.
On Tuesday, the full results of a worldwide human trial of the drug, called lecanemab, will be released at an Alzheimer’s research conference in San Francisco.
The companies — Biogen of the U.S. and Eisai of Japan — have so far merely summarized the results of the human trial in a September news release. It said early-stage Alzheimer’s disease patients who received lecanemab over the study’s 18-month timeframe scored 27 per cent better on cognitive tests than those who’d received a placebo.
More than 600,000 Canadians are living with dementia, and Alzheimer’s disease is the most common form. The Alzheimer’s Society of Canada forecasts that number to reach one million by 2030.
While some experts say there is plenty of optimism to be found about lecanemab’s potential, other have cautions and questions: What will the full data reveal? How much will the drug cost? How long can it stave off the devastating effects of Alzheimer’s disease, which can include severe memory loss, mood changes and the inability to perform basic tasks.
Roughly translated, the results suggest lecanemab slowed the advance of Alzheimer’s disease in its early stages by four-to-five months over the 18-month period of the study.
“We’ve had many failures and disappointments in drug development in this disease,” said Dr. Sharon Cohen, medical director of the Toronto Memory Clinic, one of the human trial sites for lecanemab.
“This is a very hopeful time in Alzheimer’s disease,” Cohen said in an interview with CBC News. “We have, for the first time, an opportunity to slow down a bad disease at an early stage when people are still functioning well.”
Cohen will be one of the researchers presenting the lecanemab data on Tuesday at the Clinical Trials on Alzheimer’s Disease conference.
“Any slowing of disease — if what you’re doing today you’re still doing in six months or a year — that’s a win, because we know this disease is relentless,” Cohen said. “We have not been able to stop it from progressing previously.”
‘A lot of money for 27 per cent improvement’
The news release by Biogen and Eisai described the finding that the drug slowed cognitive decline by 27 per cent as “highly statistically significant.”
But some are questioning how significant that would be for people living with early-stage Alzheimer’s.
Dr. John Forsayeth, a professor emeritus of neurosurgery at the University of California in San Francisco who has worked with biotechnology companies in the search for Alzheimer’s therapies, is skeptical about lecanemab.
“I don’t think it’s in the health-care system’s interest to spend … a lot of money for a 27 per cent improvement,” said Forsayeth in an interview. “If it really had a gigantic effect then you could make an argument.”
While the price of lecanemab has not been announced, a similar drug called aducanumab — also developed by Biogen and Eisai — hit the market last year at a cost of $56,000 US per year.
WATCH | Debate over risks and benefits of Aduhelm:
The U.S. Food and Drug Administration gave Aduhelm accelerated approval in June 2021, despite little-to-no evidence that it actually slowed the progression of Alzheimer’s. (Neither Canadian nor European regulators approved the drug.)
Aduhelm’s U.S. launch fizzled when many health insurance companies and hospitals balked at paying for the drug, saying it simply wasn’t an effective treatment. The final nail in its coffin came in January when the U.S. Medicare system refused to cover it outside clinical trials.
Biogen and Eisai have also submitted lecanemab for accelerated FDA approval and a decision is scheduled for early January.
Is drug’s target the actual cause of Alzheimer’s disease?
Lecanemab and aducanumab work in similar ways. Both are monoclonal antibodies (that’s why their names both end in -mab) and both target a protein called amyloid.
Because the brains of people with Alzheimer’s disease have abnormal clumps of this protein around and between neurons, there’s broad scientific consensus that amyloid plays some sort of role in the disease.
But there’s no consensus on what exactly that role is.
In the simplest terms, the question is whether those amyloid clumps are the root cause of Alzheimer’s disease or simply an effect. Even among those who believe amyloid does cause the disease, there’s debate over precisely how.
The hypothesis that amyloid causes Alzheimer’s dominates the field and drives the vast bulk of pharmaceutical research. Yet until lecanemab, every experimental drug that succeeded in blocking amyloid production failed to slow cognitive decline.
“This is a complicated disease. We will need a cocktail of treatments. It won’t all be about amyloid lowering,” said Cohen.
Drugs like lecanemab “will have to be complimented, augmented by other agents before we actually get the therapeutic cocktail that’s actually going to work for this devastating disease,” said Dr. Donald Weaver, senior scientist at the University Health Network’s Krembil Brain Institute in Toronto.
“The brain is the most complex entity in the universe, and arguably Alzheimer’s is the most complex disease of the brain,” Weaver said in an interview. “So the fact that we have failed, and failed, and failed is not surprising.”
He contrasts treating Alzheimer’s disease with treating high blood pressure, a condition that he describes as mechanistically far simpler.
“There isn’t one pill for high blood pressure,” said Weaver. “So why do we expect there’s going to be one magic bullet, one pill that’s going to be the cure for Alzheimer’s disease? I think that’s naive.”
The search for an Alzheimer’s treatment in Weaver’s lab is driven by his theory that amyloid is not just an evil toxin but functions as part of the brain’s immune system.
In Weaver’s theory, amyloid triggers Alzheimer’s when its infection-fighting purpose gets misdirected. “In its search and destroy mission to try to find bacteria, it cannot tell bacteria from brain cells, and so it starts to inadvertently kill brain cells,” he said.
This has Weaver aiming to develop drugs that modulate amyloid, rather than eliminate it, as done by monoclonal antibodies like lecanemab.
“I look at it like a thermostat and we’re turning [amyloid] down, turning it down so it’s not quite so hostile towards brain cells,” he said.
In addition to Weaver’s idea that Alzheimer’s is an auto-immune disease, other researchers are focused on its links to diabetes, or investigating a host of possible environmental and health risk factors.
7th leading cause of death worldwide
Dr. Saskia Sivananthan, chief science officer at the Alzheimer’s Society of Canada, said there’s no doubt that multiple treatments will be needed.
“We’re not very far along and not as far as we should be given the impact of this disease,” said Sivananthan. She attributes that lack of progress in part to the small share of research done on Alzheimer’s relative to such diseases as diabetes and cancer.
Alzheimer’s disease is the seventh-leading cause of death globally, but accounts for less than 1.5 per cent of the worldwide output of health research, according to the World Health Organization.
Still, others are hopeful about the new drug. Among them is Lorraine Klein, one of the 1,795 worldwide participants in the human trial for lecanemab.
Every two weeks starting in 2020, Klein made the 90-minute journey from her home in Cobourg, Ont., to the Toronto Memory Clinic to receive an intravenous infusion, not knowing if it was the drug or a placebo.
She still doesn’t know, but now that the research phase of the trial is over, she is definitively on lecanemab.
“I’m very happy about that, might get rid of the amyloid protein in my brain,” Klein said as the lecanemab IV flowed into her bloodstream.
Klein, 73, works as a grocery store cashier and says she found herself unable to remember the number codes for certain vegetables. Cognitive tests and a brain scan confirmed the early stages of Alzheimer’s, making her eligible for the lecanemab study.
“In the beginning, I was really afraid,” Klein said, adding that her biggest fear is forgetting her husband. “I’ve been married 54 years. I can’t imagine not remembering him.”