Treating Alzheimer’s patients as early as possible — when symptoms and brain pathology are mildest — provides a better chance of slowing cognitive decline, suggests a large study of an experimental Alzheimer’s drug presented Monday.

The study of 1,736 patients reported that the drug, donanemab, made by Eli Lilly, can modestly slow the progression of memory and thinking problems in early stages of Alzheimer’s, and that the slowdown was greatest for early-stage patients when they had less of a protein that creates tangles in the brain.

For people in that earlier stage, donanemab appeared to slow decline in memory and thinking by about four and a half to seven and a half months over an 18-month period compared to those taking a placebo, according to the study. published in the journal JAMA. Among people with less of a protein called tau, slowing was most pronounced in those younger than 75 and those who did not yet have Alzheimer’s but had a pre-Alzheimer’s disease called mild cognitive impairment, according to data presented Monday at the Alzheimer’s Association International . Conference in Amsterdam.

“The sooner you can get in there, the more you can impact it before they’ve already declined and they’re on this rapid decline,” said Dr. Daniel Skovronsky, Eli Lilly’s chief medical and scientific officer, in an interview.

“No matter how you slice the data – earlier, younger, milder, less pathology – every time, it seems that early diagnosis and early intervention is the key to managing this disease,” he added.

The findings and the recent approval of another drug that modestly slows decline in the early stages of Alzheimer’s, Leqembi, signal a potentially promising turning point in the long, rocky road to finding effective drugs for Alzheimer’s, a devastating disease that afflicts more than six million Americans. . . Donanemab is currently being considered for approval by the Food and Drug Administration.

Donanemab and Leqembi (also known by the scientific name lecanemab) have not been compared directly to each other in research studies. The individual trials of the two drugs differ in design and other aspects, making it difficult to say which drug might be more effective.

Each drug poses significant safety risks, particularly swelling and bleeding in the brain, which, although often mild, can be serious in some cases. The donanemab trial had higher rates of swelling and bleeding than the Leqembi trial, but comparisons are difficult because of differences in patients and other factors.

Neither drug reverses or repairs brain damage already caused by the disease. Many Alzheimer’s experts therefore consider them only a first step in a potentially fruitful direction.

“Whether the harms of these drugs are balanced by their modest clinical benefits will ultimately require more data,” wrote three geriatricians in editorial published Monday in JAMA.

Three deaths were linked to donanemab in its clinical trial, the study reported. Three participants in Leqembi’s trials also died, after experiencing brain swelling and bleeding. But Eisai, the Japanese company that makes Leqembi along with Boston-based Biogen, said it was unclear whether the drug contributed to those deaths because those patients had complex medical problems.

The two drugs attack another protein, called amyloid, that builds up into plaques in the brains of Alzheimer’s patients. Over years of study, other anti-amyloid drugs have not shown that targeting amyloid could slow memory or thinking problems. And the FDA’s decision in 2021 to give a kind of conditional approval to the anti-amyloid drug Aduhelm while acknowledging uncertainty about whether it was useful generated controversy, congressional investigations and a reluctance to prescribe it.

Donanemab and Leqembi, infusions that are administered intravenously, are the first amyloid-attack drugs with clear evidence of slowing cognitive decline early in the disease. But some Alzheimer’s experts say the slowdown is so modest that it’s unclear whether it will be noticeable to patients and families.

Leqembi patients who received infusions every two weeks for 18 months declined 27 percent more slowly than patients receiving a placebo—a difference of less than half a point on an 18-point cognitive scale that assesses functions such as memory and problem-solving. On the same scale in the donanemab trial, the overall group of patients receiving the drug, delivered in monthly infusions, declined 29 percent more slowly than the placebo group—or a difference of seven-tenths of a point.

Some Alzheimer’s experts say that for a slowing of decline to be clinically significant or visible, the difference between a drug and a placebo must be at least one point.

Other aspects of the donanemab trial are likely to be of particular interest to Alzheimer’s experts. Patients stopped receiving donanemab and were switched to placebo if their amyloid was cleared below a certain threshold. About half reached the threshold within a year, and their decline continued to slow even after they stopped receiving donor amab.

Lilly scientists estimated that it would take almost four years so that amyloid levels rise above the threshold again. It is uncertain whether a slowing of decline would continue when amyloid begins to accumulate again.

The donanemab trial divided participants into patients with high levels of tau and those with intermediate levels. Tau forms tangles after amyloid accumulates, and higher tau levels are more closely associated with memory and thinking problems.

The test found that the medium group (which was larger) experienced a 36 percent slowing of decline, compared to 29 percent for the combined medium and high tau groups and 21 percent in the high tau group alone. Another scale, which was the primary measure of the test, showed the same pattern. Lilly calculated that decline for patients in the median group would be slowed by 4.4 to 7.5 months over 18 months compared to people on placebo, while the combined population would see a slowdown of 2.5 to 5.4 months.

More people with moderate tau remained at the same cognitive level in their first year in the trial – 47 percent compared to 29 percent of people in the placebo group, the study estimated. In the combined tau groups, 36 percent of people on donanemab stayed at the same level compared to 23 percent of people on placebo.

In the intermediate tau group, donanemab patients with mild cognitive impairment slowed by 46 percent, while those who had already progressed to early Alzheimer’s slowed by 38 percent, the company reported. Average tau patients who were younger than 75 slowed by 45 percent, while older patients slowed by only 29 percent.

One criticism of the study was that, as in many Alzheimer’s trials, a vast majority of patients were white, a concern highlighted by the authors of another editorial in JAMAwho noted that black, Hispanic and other historically marginalized communities have higher risks of Alzheimer’s.

The difficulty of predicting whether these drugs will be relevant in everyday life is reflected in the experience of a patient in another trial of donanemab.

About four years ago, Jim Sirois, 67, of Berlin, Conn., began having trouble finding words during conversations and would forget which items to buy at the grocery store, his wife, Sue Sirois, said in an interview arranged by Eli Lilly.

In November 2021, Mr. Sirois, a former power company electrician, began receiving monthly donanemab infusions in judgment comparing whether the drug clears more amyloid than the drug Aduhelm does. Ms. Sirois, a former high school math teacher, said donanemab cleared the plaques and that treatment was stopped after about 13 months. But the couple said they did not know whether the medication had slowed Mr. Sirois’ cognitive decline.

Although her husband’s symptoms did not worsen significantly, Ms. Sirois said, “there were some things that he was able to do without problems last summer that he is having difficulty doing this summer.”

Mr. Sirois is now unable to hook up their pool vacuum or insert a cord into their beater. “He just has a lot of difficulty with planning and anything that has multiple steps,” she said.

Even bowling, an activity he excels at, was affected. His aim may be less on target now and, although he has bowled a perfect game recently, “his average is probably a good 20 pins lower than it used to be,” she said.

“I don’t know if the drug helped him or not,” Ms. Sirois said. “I can’t say.”

But, she added, “Whatever we can do to slow the progression or at least have some hope of slowing the progression is what I would want to do.”

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