Earlier this week, pharmaceutical companies Biogen and Eisai announced promising results from clinical trials in people with Alzheimer’s disease. A monoclonal antibody treatment called lecanemab reduced cognitive decline in early Alzheimer’s disease patients by 27% compared to a placebo group. A year and a half later. Outside observers say the trial could offer hope to some of the millions of people suffering around the world.

But amidst the excitement, many questions remain, such as why this treatment holds promise when other treatments based on similar strategies have failed. have attempted to target the buildup of amyloid plaques in the brain that are characteristic of Amyloid, clumps of protein that destroy neurons and other cells. The new treatment is apparently the first to do so.

This area is embroiled in controversy. Another Biogen drug, aducanemab, was approved by the Food and Drug Administration (FDA) last year over concerns that the evidence that it relieves patients’ symptoms, despite clearing out amyloid plaques, is not convincing. Other approved Alzheimer’s disease treatments target the presumed root of the disease and only its symptoms. Prior to aducanumab, U.S. authorities hadn’t greenlit an Alzheimer’s drug for nearly 20 years.

chemistry We spoke with Alzheimer’s disease experts about this week’s announcements and the future of lecanemab and the field.

What did clinical trials find?

In a press release, Biogen and Eisai shared the results of a trial involving 1,795 people with early Alzheimer’s disease. Participants were randomized to receive either lecanemab or placebo intravenously every other week for 18 months. The primary test was to compare cognitive decline between the two groups based on the classic dementia scale called the Clinical Dementia Rating-Sum of Boxes (CDR-SB). “I grew up with it and love it,” says Joy Snyder, a neurologist at Washington University in St. Louis, of the assessment tool developed at her institution. She heads the clinical trials arm of the Knights Alzheimer’s Research Center there, and has enrolled nine of her patients in the lecanemab study. One of the benefits of the assessment, Snyder said, is that it includes information from family members about how the patient is living, as well as other measurements.

In this study, people who received lecanemab still had cognitive decline, but progressed 27% slower than those who received placebo. is converted to It’s a slight difference, but I’m hoping for spawning. “This makes us feel a little better. These drugs work,” Snyder says.

Lecanemab had side effects. Most prominent are certain brain abnormalities seen with other anti-amyloid therapies, such as brain swelling and minor hemorrhages. Neuroimaging revealed these concerns in approximately 21% of patients on lecanemab and 9% of his on placebo. These abnormalities are often asymptomatic, but approximately 3% of patients receiving lecanemab did.

Doctors aren’t sure how the gradual slope of cognitive decline will be perceived by patients and their families. You mean?” asks Jonathan Jackson, a cognitive neuroscientist at Massachusetts General Hospital (MGH). “It’s still an open question.” “We’re all feeling cautious and cautious,” says Jackson. “I like to dig into the data before making big conclusions.”

Why did this drug hit its mark when other drugs failed?

No one knows for sure, but there are some theories. One is that lecanemab works a little differently than other anti-amyloid drugs. “When amyloid clumps into these large plaques, some people try to bind or remove it,” Jackson says. Aducanemab primarily binds to amyloid proteins after aggregation. Lecanemab, on the other hand, swoops in earlier and targets ‘protofibrils’, strands that have not yet solidified into plaque. Evidence from many trials and other studies suggests that the earlier in the disease process tracking amyloid plaques is the better. said, “It was always something we had a lot of hopes for.”

Also, the longer trial duration of lecanemab made it easier to detect differences between patients who did not receive experimental treatment and those who did. Assuming Alzheimer’s drugs work, the effect “will be greater the longer the trial goes on,” says Bert de Struper, director of the UK Dementia Research Institute. In fact, Biogen and Eisai noted that lecanemab had no significant effect on his cognition after 12 months, but had a significant effect at 18 months.

The trial only included people with evidence of amyloid in their brains. Mr. De Strooper said.

Is a diverse study population important?

One of the notable features of the lecanemab trial was that approximately 25% of the participants were black or Hispanic. “We like to think that people have equal access to our science, but that’s often not the case,” said Jason Karlawish, co-director of the Penn Memory Center at the University of Pennsylvania.

Additionally, these populations are at higher risk of Alzheimer’s disease than non-Hispanic whites, and researchers don’t fully understand why. “We want a drug that works for everyone,” says Snyder.

For Jackson, who studies the impact of diversity and inclusion in human subjects research and directs the Center for Community Access, Recruitment and Engagement Studies at MGH and Harvard Medical School, the new trial population represents an opportunity to study this disparity. provide. One theory is that black and Hispanic people may be at higher risk of dementia because they have higher rates of diabetes and cardiovascular disease, which can affect the brain, he explains. Examining how well lecanemab (“an anti-amyloid therapy that truly focuses on the pure symptoms of Alzheimer’s disease”) worked in black and Hispanic participants will provide biological insight into their disease. “We believe this will be the first opportunity to have sufficient data on ethnic and racial minorities in Alzheimer’s trials,” says Jackson.

What impact will Alzheimer’s have on the field?

Lecanemab is “not a cure, it’s not going to make people better,” warns Snyder. (Nevertheless, scientists warn that they would feel more comfortable if companies released more complete trial data, especially after their experience with aducanumab.)

Other anti-amyloid antibodies are in trials, and De Strooper said he would like to see the development of small-molecule drugs that can be swallowed instead of injected. But Jackson hopes that “a new treatment coming out in three or four years has the potential to achieve that goal by far.” Better performance could come from researchers learning how to build better and safer anti-amyloid therapies and determining who is best suited to receive them, he said. increase.

That said, “I don’t think we can just focus on amyloid just yet,” Snyder says. Future anti-amyloid treatments may or may not be better than this. “This drug may work as well as we can,” she says. This is especially true for those who already have symptoms. “We don’t treat cancer with her one drug, we drink cocktails,” she says. Physicians need a similarly diverse toolkit for Alzheimer’s disease, where inflammation and other factors are also important contributors.

What questions do you have?

many! First, researchers would like to see more data from the lecanemab trial, which is expected to be released in late November. Given that, there is a lot of interest and anxiety about how the deployment of lecanemab will proceed in the real world. I suspect that people who take it may have a higher risk of brain hemorrhage from lecanemab.

Karlawish wants more information about how patients are doing in the long term. At this point, assuming the company’s announcements are consistent with their trial data, the treatment appears to be “worth taking,” or at least worth considering for those for whom it was designed. However, “the big question in clinical practice is how well a drug works and how long it should last.” Karlawish is looking at registries that track people undergoing treatment to help guide doctors and families facing difficult choices. I think I want to do. “We don’t have enough workforce to deploy this drug and similar drugs to clinical practice,” he says.

Lecanemab is now being tested in people with evidence of amyloid—And it is often a familial or genetic risk factor, but without symptoms. The compelling question is whether treatment can stem dementia: De Strooper says he should show subtle signs of the disease at least 10 years before obvious symptoms appear. Preventing their deterioration is another frontier.