Breakthrough in Alzheimer’s research: examining the pros and cons of two promising new drugs

Alzheimer’s disease is complex and unlikely to ever be successfully treated in all people living with the disease with any one drug or other intervention. However, this hasn’t stopped researchers in their pursuit to find a drug that reverses its progressive destruction of memory and thinking skills and, should the patient live long enough, much worse. This article discusses the pros and cons of two new drugs for treating Alzheimer’s disease: lecanemab and donanemab, noting that other approved treatments for Alzheimer’s only boost mental functioning temporarily without targeting the underlying problem of neuron destruction. While both new drugs, unfortunately, present only modest benefits, not to mention their not insignificant potential negative effects, their emergence does offer a rare but real sense of hope for the field of Alzheimer’s research. – Nadya Swart

The Pros and Cons of New Drugs to Treat Alzheimer’s Disease

By Robert Langreth

While humans are living longer –­ a child born in 2021 on average could expect to live to 71 –­ we haven’t figured out how to beat one of the worst scourges of ageing: Alzheimer’s disease. Afflicting an estimated 36 million people worldwide, it’s the most common form of dementia, a loss of cognitive functioning severe enough to interfere with daily life. 

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Researchers have yet to find a drug that reverses its progressive destruction of memory, thinking skills, and the ability to swallow and breathe if sufferers live long enough. Two new treatments have emerged that slow the rate at which patients decline. They do that modestly and come with downsides. Still, their success has provided a rare burst of hope for the field of Alzheimer’s research. 

1. What causes Alzheimer’s

It’s not clear. Researchers think that the buildup of abnormal proteins seen in the brains of Alzheimer’s patients plays a central role. One, called amyloid, forms so-called plaques around brain cells. Their presence alone doesn’t seem to trigger cognitive decline, given that some people with normal mental functioning have them. A second protein, tau, creates tangles within brain cells. And a third suspect, brain inflammation, is thought to contribute in some way, perhaps in an intermediary role. Whatever the precise mechanisms, over time, neurons – cells that send messages throughout the brain and the rest of the body – stop working and die.

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2. What do the new treatments do?

The drugs, both laboratory-made antibodies, are lecanemab — sold under the brand name Leqembi — from Eisai Co. and Biogen Inc., and donanemab from Eli Lilly & Co. In trials, each significantly reduced the brain amyloid levels of Alzheimer’s patients in the early stages of the disease. More important, the patients’ cognitive declines slowed. After 18 months, those given lecanemab had scores 27% better than those given a placebo on a scale that measures six capacities — memory, orientation, problem-solving, function inside and outside the home, and personal care. In the donanemab trial, the figure was 29% for all trial participants and 36% for a subset with lower levels of tau protein.

Alzheimer's
Alzheimer's

3. Who can take these drugs?

The US Food and Drug Administration initially cleared lecanemab in January, and its developers have filed for approval in the European Union, Japan and China. Donanemab’s positive trial results in May paved the way for its developer to apply for US approval. The drugs were proven effective only in people in the early stages of the disease when cognition and functioning are mildly impaired. Their use is likely to be further limited by the need to be tested first for signs of brain amyloid. An amyloid PET scan is one method, but it’s expensive, often unavailable, and, in the US, rarely covered by insurance. Another option is a spinal tap, in which a needle is inserted between two vertebrae to collect cerebrospinal fluid, but it’s an invasive and sometimes painful procedure. A few blood tests sold in the US can indicate whether amyloid is present in the brain, but none are routinely covered by insurers or cleared by the FDA. Japan’s health ministry approved such a test in late 2022. 

4. What are the limitations of the drugs?

In the trials, the patients on them still declined, just somewhat more slowly than those who didn’t take it. A significant drawback is that the drugs can cause brain swelling and bleeding. More than a fifth of people who took lecanemab experienced these effects, and the figures were higher for donanemab. In most cases, these patients didn’t experience any related symptoms, but some had headaches, visual disturbances and confusion. In the donanemab trial, three participants died after experiencing these side effects, while in the lecanemab study, five developed large brain haemorrhages. The trials enrolled between 1,700 and 1,800 people, split between groups that received the drug and a placebo. The two drugs are administered as intravenous infusions — every two weeks for lecanemab and every four weeks for donanemab — which means patients must receive them at a health centre. Lecanemab is expensive — $26,500 per year in the US — and Eli Lilly has said it expects a similar price for donanemab.

5. Are there other Alzheimer’s drugs?

handful of approved treatments modestly boost mental functioning temporarily in some patients, but they don’t target the underlying problem: the destruction of neurons. That was the aim of an earlier treatment from Biogen and Eisai, Aduhelm, which also was designed to reduce amyloid. It was approved by the FDA in 2021 despite conflicting trial results. The approval sparked controversy, and Aduhelm’s makers eventually stopped marketing the drug in the US.

6. What are the future paths for Alzheimer’s research?

The latest trial results strengthened the view that researchers are on the right track focusing on treatments that clear away amyloid. Still, it’s not yet clear why lecanemab and donanemab succeeded where similar drugs failed. Some researchers suspect that a certain threshold of amyloid removal must be met before a drug produces benefits. But with the payoff limited even to those in the early phase of Alzheimer’s – possibly because damage to key brain areas is already extensive – some researchers are focused on getting ahead of the disease. Brain scan studies suggest that amyloid starts accumulating as long as two decades before someone has dementia. In trials sponsored by Eli Lilly and Eisai, researchers are testing amyloid-removing drugs on thousands of healthy adults. The hope is to stave off cognitive decline before it begins or at least delay it. Meanwhile, researchers are also developing drugs that target tau and brain inflammation.

The Reference Shelf

  • Bloomberg columnist Lisa Jarvis explores the value of lecanemab.
  • The US National Institute on Aging aggregates information on Alzheimer’s disease, its symptoms, diagnosis and treatment.
  • Alzheimer’s Disease International’s 2021 report.
  • Alzforum is a web-based scientific community dedicated to understanding Alzheimer’s disease and related disorders.

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