A large study of experimental Alzheimer’s drugs, released Monday, suggests that treating Alzheimer’s patients as early as possible — when symptoms and brain pathologies are at their mildest — may slow cognitive decline. suggests an increase.
In this study of 1,736 patients, a drug called donanemab, made by Eli Lilly, could slow the progression of memory and thinking problems in the early stages of Alzheimer’s disease to some extent, and early-stage patients had no symptoms. It was reported that the slowness was greatest in the light case. A protein that causes tangles in the brain.
According to the study, in those in its early stages, donamab appeared to slow the decline in memory and thinking ability by about four and a half months to seven and a half months over a period of 18 months compared to those who took a placebo. It is said that Published in JAMA magazine. Data released Monday at the International Alzheimer’s Association showed that among people low in a protein called tau, the slowdown was most pronounced in people under the age of 75 and those who didn’t yet have Alzheimer’s disease. There were no people with a pre-Alzheimer’s disease condition called mild cognitive impairment. Conference in Amsterdam.
“The sooner we can get in there, the more impact we can have before the patient numbers are already down and steep,” said Dr. Danielle Skovronski, Eli Lilly’s chief medical and scientific officer, in an interview. I can do it,” he said.
“Early diagnosis and early intervention appear to be key to managing this disease, no matter how you slice the data — early, young, mild, or declining disease,” he added.
This discovery, along with the recent approval of Rekembi, another drug that gently slows the progression of symptoms in the early stages of Alzheimer’s disease, is an effective treatment for Alzheimer’s disease, a brutal disease that afflicts more than 6 million Americans. It suggests a possible bright turn on the long and arduous road to drug discovery. . Donanemab is currently under consideration for approval by the Food and Drug Administration.
Donanemab and lequembi (also known as lecanemab) have not been directly compared to each other in research studies. Individual trials of the two drugs differed in design and other aspects, making it difficult to say which drug was more effective.
Each drug poses significant safety risks, especially brain swelling and bleeding, which are often mild but can be serious in some cases. The rate of swelling and bleeding was higher in the donanemab trial than in the Lekembi trial, but comparisons are difficult because of differences in patient numbers and other factors.
Neither drug reverses or repairs brain damage already caused by the disease. Therefore, many Alzheimer’s disease experts see these as just the first steps in a potentially fruitful direction.
“Whether the harms of these drugs are balanced with modest clinical benefits will ultimately require more data,” three geriatricians wrote. . editorial It was published in JAMA magazine on Monday.
The study reported that three deaths in clinical trials of donanemab were related to donanemab. Three participants in the Lekembi trial also died from brain swelling and hemorrhage. However, Eisai, the Japanese company that manufactures Rekembi along with Boston-based Biogen, said these patients had complicated medical problems, so it is unclear whether the drug contributed to these deaths. said.
The two drugs attack another protein called amyloid that clumps together into plaques in the brains of people with Alzheimer’s disease. Years of research have shown no other anti-amyloid drugs can slow memory and thinking problems by targeting amyloid. And the FDA’s decision in 2021 to grant some sort of conditional approval to the anti-amyloid drug Aduhelm while acknowledging uncertainty about its benefits has sparked controversy, congressional investigations, and reluctance to prescribe. .
Intravenous donanemab and lekumbi infusion are the first amyloid-attacking drugs to provide clear evidence of slowing cognitive decline in the early stages of disease. But some Alzheimer’s experts say the slowdown is so gradual that it’s unclear whether patients and families will be able to recognize it.
For 18 months, Rekumbi patients who received an infusion every two weeks had a 27 percent slower decline than those who received a placebo. The difference was less than 0.5 points on an 18-point cognitive scale that assesses functions such as memory and problem-solving. On the same scale of the donamab trial, the overall group of patients who received the drug as a monthly infusion declined 29 percent more slowly than the placebo group, a difference of 7-ten points.
Some Alzheimer’s disease experts say the difference between the drug and placebo must be at least 1 point to delay a clinically meaningful or noticeable decline.
Other aspects of the donanemab trial may be of particular interest to Alzheimer’s disease professionals. Patients were discontinued from donemab and switched to placebo if amyloid fell below a certain threshold. Approximately half reached threshold within 1 year, and the decline continued to slow after stopping donemab.
Lilly scientists estimate that it will take time. almost 4 years The amyloid level crosses the threshold again. It is unclear whether the slowing of decline will continue as amyloid begins to accumulate again.
In the donamab trial, participants were divided into those with high levels of tau and those with moderate levels of tau. Tau forms tangles after amyloid builds up, and higher tau levels are more closely associated with memory and thinking problems.
In this study, the intermediate group (larger body) slowed decline by 36%, compared with a 29% decline in the combined intermediate and high-tau group and a 21% decline in the high-tau group alone. It has been found. Another scale, which was the primary measurement tool in the study, showed the same pattern. Lilley said that the decline in the intermediate group of patients was 4.4 to 7.5 months slower at 18 months compared to those who received placebo, but he was 2.5 to 5.4 in the combined population. I calculated that it will drop for a month.
The study estimated that the majority of people with intermediate tau maintained the same level of cognition during the first year of the trial, 47 percent compared with 29 percent of people in the placebo group. In the tau combination group, 36% of those who received donanemab maintained the same levels, compared to 23% of those who received placebo.
In the intermediate tau group, patients with mild cognitive impairment with donanemab experienced a 46% reduction in velocity, while those who had already progressed to early Alzheimer’s disease experienced a 38% reduction in velocity, the company reported. Intermediate tau patients under the age of 75 experienced a 45 percent reduction in velocity, while older patients experienced a reduction of only 29 percent.
One criticism of the study, as with many Alzheimer’s drug trials, is that the majority of patients are white, and the authors of another JAMA editorial underscored this concern, noting that blacks, Hispanics and other historically marginalized communities are at higher risk of Alzheimer’s disease, he said. Alzheimer’s disease.
The difficulty in predicting whether these drugs will make sense in everyday life is reflected in patient experience in another trial of donamab.
About four years ago, Jim Sirowa, 67, of Berlin, Connecticut, began having trouble finding words in conversations and forgetting what to buy at the grocery store. His wife, Sue Shirowa, said in an interview organized by Eli Lilly.
In November 2021, Mr. Shirowa, a former power company electrician, began taking a monthly drip of donanemab. trial Compare whether this drug clears more amyloid than Aduhelm. Shirowa, a former middle school math teacher, said that donanemab cleared plaques and stopped treatment after about 13 months. But the couple said they don’t know if the drug slowed Shirowa’s cognitive decline.
Her husband’s condition hasn’t gotten any worse, but Shirowa said, “There are some things that were fine last summer that have become difficult this summer.”
Shirowa currently cannot hook up a pool cleaner or insert a thread into a weed beater. “He’s bad at planning and taking multiple steps,” she says.
His specialty, bowling, is also affected. His aim is now less targeted. Although he recently hit a perfect game, “his average is probably about 20 pins lower than it used to be,” she says.
“I don’t know if the drug worked for him,” Shirowa said. “don’t understand.”
But she added, “Anything I can do to slow it down, or at least if there is any hope of slowing it down, that’s what I want to do.”