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According to the National Institute on Aging, heart attacks and strokes are the biggest risks for senior citizens, but the disease seniors fear most is dementia. By far the biggest cause of dementia is Alzheimer’s disease. What happens when a person has Alzheimer’s dementia is an irreversible and progressive loss of memory and thinking skills, called cognitive decline. There have been drugs that help a person with Alzheimer’s disease get the best out of the cognitive ability they have left, but until now, no drug has clearly shown the ability to slow progression of cognitive loss.
In January 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval for lecanemab, with the brand name Leqembi. The approval is based on the results of a phase 3 randomized, placebo-controlled clinical trial. Phase 3 is the final phase of testing needed for a new drug approval, and randomized placebo-controlled trials are the gold standard for drug testing. The trial was presented at the Clinical Trials for Alzheimer’s Disease Conference in November and published in The New England Journal of Medicine.
Lecanemab (Leqembi) is a new type of drug called an anti-amyloid antibody. Dementia from Alzheimer’s disease is caused by a type of protein that builds up in the brain and destroys brain cells called neurons. The protein is amyloid beta and collections of this protein in the brain are called amyloid plaques. Imaging studies of the brain in people with Alzheimer’s disease show that amyloid plaques increase as cognitive loss increases. Other proteins called tau also increase, and are called tau tangles. Why these plaques and tangles form remains a mystery.
Leqembi is laboratory designed antibody, called a monoclonal antibody. Antibodies are proteins that your body’s defense system – your immune system – uses to fight off foreign invaders like viruses or bacteria. Antibodies can bind to foreign invaders and keep them from doing damage. Anti-amyloid antibodies are created to bind to amyloid proteins in the brain and prevent them from killing neurons.
The Leqembi Trial
The trial used to approve Leqembi lasted 18 months. It took place at 235 sites in the United States, Europe, and Asia. The first goal of the trial was to show that patients taking the new drug would have a significant slowing of cognitive decline. To do this they used a test called the Clinical Dementia Rating scale. Other important goals were to show actual slowing of amyloid plaque formation with brain imaging studies, and less decline on an Alzheimer’s disease assessment scale that measures activities of daily living.
All the people in the trial had early Alzheimer’s disease diagnosed with brain imaging and cognitive testing. There were about 1,800 people in the study. Half of the patients got the actual drug and half got an inactive placebo. Neither the patients or the researchers knew which patients got a placebo or the drug.
At the end of the study, patients who got the drug had 27 percent less decline on the clinical dementia scale than the placebo group. They also had significantly fewer amyloid plaques on their brain scans compared to the placebo group. The drug slowed decline on the activities of daily living scale by 37 percent compared to the placebo group. The benefits of the drug started to show up after 6 months of treatment.
Another important part of any drug approval trial is safety. Unwanted side effects in clinical trials are called adverse events, and adverse events were 13 percent more common in the drug group than the placebo group. Although six people taking the drug died during the trial, seven people taking the placebo also died, and there was not enough evidence to say the drug caused the deaths in the drug group.
According to the FDA approval news release, the accelerated approval was based mainly on the reduction of amyloid plaques seen on brain scans of the patients taking the drug. Leqembi is given as an intravenous infusion every other week. The FDA has placed a warning in the prescribing information about temporary swelling of the brain and small spots of bleeding on the surface of the brain. These adverse events usually cause no symptoms and go away. Possible adverse symptoms may include headache, confusion, dizziness, and flu-like reaction to the infusion. The FDA has approved Leqembi for patients with early Alzheimer’s disease or mild cognitive impairment.
Other Drugs for Alzheimer’s Disease
Leqembi is not the only anti-amyloid antibody being used for Alzheimer’s disease. Aducanumab (Aduhelm) was approved by the FDA because it was shown to reduce amyloid deposits, but it has not shown the ability to slow progression. Older drugs called cholinesterase inhibitors increase a brain messenger, called a neurotransmitter. They may reduce symptoms in early Alzheimer’s. Memantine is a drug that increases a different neurotransmitter, and can be used for more severe symptoms. These medications have been around since the 1990s and they do not slow down the disease but they help healthy neurons work better while they can.  More anti-amyloid antibodies are coming. The next one is called donanemab, and early reports from the trials are encouraging.
The doctors who did the Leqembi trial concluded that it slows decline in thinking and functioning in early Alzheimer’s disease. The Alzheimer’s Association says, “The results of the trial show that this treatment may change the course of early Alzheimer’s disease in a meaningful way and give people more time to remain independent and participate in daily life.” Time will tell if these anti-amyloid antibodies will be the major breakthrough in Alzheimer’s treatment that people have been hoping for.
Until then, you should know that research shows you can significantly reduce your risk of Alzheimer’s disease with a healthy lifestyle. This includes a heart-healthy diet (also good for brain health) and regular exercise, not smoking and using alcohol only in moderation. As you age you can build extra brain power by challenging your brain with new activities and learning skills. Some studies show that this brain power, called cognitive resilience, may delay cognitive decline, even in people with early Alzheimer’s brain changes.