The Latest Alzheimer’s Drugs to Slow Down Progression of the Disease – And Top Ways to Prevent It

For years, people who were concerned about forgetfulness, senior moments and possible mild cognitive impairment didn’t want to know for sure whether they were experiencing normal signs of aging or early Alzheimer’s. 

Typically, they’d say, “What’s the point of finding out if I have Alzheimer’s if nothing can be done about it? Besides, they’ll probably just take away my driver’s license.”

Nevertheless, professionals advised, “Better to know as soon as possible so you can make plans for the future.” If the diagnosis was indeed Alzheimer’s, that future was not pleasant to contemplate.

But now there’s the best reason of all for diagnosing Alzheimer’s as early as possible. Two drugs have been shown this year to slow down progression of the disease when it is treated early.

Both are ‘biologics’ — monoclonal antibodies (MABs) that clear amyloid from the brain. 

In addition to clearing amyloid, these drugs consistently slowed clinical progression of the disease on multiple measures of cognition and daily functioning.

Lecanemab was shown to slow the progression of Alzheimer’s by 27 per cent on its primary outcome measure, while the newer drug, donanemab, slowed the disease by 35 per cent on its primary outcome measure. Both are given through IV infusion —  lecanemab every two weeks, donanemab every month. Subcutaneous injections (like for insulin or Ozempic) are in the works.

However, these new drugs aren’t without problems.

Lecanemab is already available in the U.S., sold as Leqembi, after being granted accelerated approval by the FDA. The full, traditional approval is expected in July. 

As well, donanemab manufacturer Eli Lilly announced earlier this month that the final Phase 3 trial was successful. They plan to file for FDA approval before the end of June.

Neither drug is available yet in Canada but it’s hopeful that Health Canada will approve lecanemab by the end of the year or early in 2024, according to neurologist Dr. Sharon Cohen, medical director and principal investigator at Toronto Memory Program. The community-based medical facility focuses on Alzheimer’s and other dementias, and offers free memory assessments and opportunities to participate in clinical trials

Dr. Cohen was one of the authors of the lecanemab study published early this year in the New England Journal of Medicine.

“With both lecanemab and donanemab, there is a reduction in the chance of moving to the next stage of the disease, says Cohen, “and that’s important.

“People will say, ‘I can manage the way I am but what I fear is getting worse, not recognizing family or being a burden.’ It’s what’s coming that’s scary and if we can slow progression to the next stage, that’s very meaningful for patients.

“And the evidence is increasing that we are making progress in slowing the disease.”

The new drugs follow the first Alzheimer’s drug approved by the FDA.

Aducanumab (brand name Adulhelm) was controversial because the evidence for its efficacy was unclear and the initial cost was around US$56,000 per year. The cost-benefit ratio led the U.S. Medicare program to cover it only for Medicare recipients in clinical trials. Its maker, Biogen, withdrew it from Health Canada review in June 2022.

 

Drug Detractors

 

The newer drugs are also not without detractors. The amount of slowing of the disease with lecanemab might not be clinically meaningful, suggested an editorial in The Lancet.

Cohen, who regularly sees patients concerned about looming impairment from Alzheimer’s, considers the value of the drugs from the human point of view rather than points on a scale.

“To quarrel that the saving is not great enough is to not understand what happens in the early stage,” she says. “If mild cognitive impairment is due to Alzheimer’s, [lecanemab] can make the difference from being able to continue to do something and no longer being able to do it.

“When we look at donanemab, we see consistent slowing of disease at the early stage, we see it slowing cognitive decline and we see an even greater magnitude in slowing of function decline. It’s about quality of life. Can people do tomorrow what they can do today?”

 

Potential Side-Effects

 

Cohen acknowledges that there are potentially serious side-effects with these biologic drugs.

MRI monitoring detected brain swelling and slight bleeding in the brains of some of the patients taking these drugs. Fortunately, most had no symptoms. When symptoms did occur, they were usually mild to moderate and resolved spontaneously. However, in rare cases they were severe. Three people in the donanemab study died from complications such as brain bleeding and seizures. 

Therefore, she says MRI monitoring of people on these drugs will be necessary, which is an extra burden to the health system.

But the biggest burden to the health system in implementing treatment for early Alzheimer’s will be diagnosing the disease at the earliest stages. Right now, only a PET scan or a lumbar puncture can definitively identify amyloid in the brain, although a blood test can predict the likelihood of amyloid. 

“We really need to have a more accessible and less expensive way of doing this than a PET scan or a lumbar puncture,” says Cohen. “We need restructuring towards early diagnosis.”

There’s also more education needed, she says, so that when people go to the doctor wondering about memory loss or symptoms of cognitive decline, they’re not told, “What do you expect when you’re 70?”

Although the restructuring for early diagnosis and high cost of biologic drugs, combined with an aging population, could add stress to the health system, Cohen suggests that early treatment would reduce institutionalization, caregiving and nursing services and emergency department visits.

 

Just the Beginning

 

These new biologic drugs that reduce amyloid in the brain are just the beginning, she says.

“We haven’t had results this good before, so now we have a foothold, catching the disease at an early stage. Now we have to build on that.”

That includes research into other factors linked to Alzheimer’s, including tau protein buildup and inflammation. “Alzheimer’s disease and other dementias are incredibly complex and more than likely have multiple players on the pathway and likely many paths that cause the disease,” explains Dr. Saskia Sivananthan, chief science officer for the Alzheimer Society of Canada.

“Lecanemab as well as the more recent news about donanemab are promising results for this first class but we need more investment to move forward with prevention and cures.” 

 

Ways to Reduce Risk

 

Meanwhile, she says, “We know a lot more about risk reduction and lifestyle changes that we have in the past. Each risk factor likely has different ways in which they can lower the risk of developing dementia.

“Our landmark study outlines this in more detail for the top 12 risk factors linked to dementia.” Top tips to keep your brain healthy include:

1. Stay physically active by finding an activity you enjoy doing on a daily basis, such as walking, gardening, weightlifting, yoga and swimming
2. Protect your heart by closely monitoring your blood pressure, cholesterol and diabetes 
3. Stay socially active
4. Manage your medical conditions — remember, better overall health is linked to better brain health
5. Challenge your thinking by trying to learn new things, no matter what your age
6. Get a good night’s sleep, typically from six to eight hours each night
7. Have depression treated
8. Avoid excessive alcohol intake
9. Monitor your hearing, and be sure to use hearing aids if you need them
10. Find meaningful work or activities
11. Try to avoid all types of head injury
12. Embrace a healthy lifestyle, including keeping to a nutritious diet, reducing stress, quitting or reducing smoking and keeping regular checkups with your doctor

 

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