Treating Alzheimer’s early can reduce disease progression – 07/18/2023 – Equilibrium

Treating Alzheimer’s patients as early as possible, when symptoms and brain pathology are milder, offers a better chance of slowing cognitive decline, suggests a large study of an experimental drug for the disease presented Monday. .

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

For people with early illness, donanemab appeared to delay the decline in memory and thinking by about 4.5 to 7.5 months over an 18-month period, compared with patients taking a placebo, according to the published study. in Jam magazine.

Among people with the lowest amount of this protein, called tau, the slowdown was most pronounced in those younger than 75 and those who did not yet have the disease but a pre-Alzheimer’s condition called mild cognitive impairment. The data were presented at the International Conference of the Alzheimer’s Association, in Amsterdam (Holland).

“The sooner you get there, the more you can impact it before they’ve already declined and are on that fast slope,” Daniel Skovronsky, chief medical and scientific officer at Eli Lilly, says in an interview.

“No matter how you break down the data — earlier, younger, milder, less pathology — it always seems that early diagnosis and intervention is the key to controlling this disease,” he adds.

The findings and recent approval of another drug that moderately slows the decline in early stages of Alzheimer’s disease, Leqembi, signal a potentially promising turn in the long and difficult road to finding effective drugs for the disease. Donanemab is currently being considered for FDA approval.

Donanemab and Leqembi (also known by the scientific name lecanemab) have not been directly compared with each other in 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 of these carries significant safety risks, especially swelling and bleeding in the brain, which, while generally mild, can be severe in some cases. The donanemab trial had higher rates of swelling and bleeding than the Leqembi trial, but comparisons are difficult because of patient differences and other factors.

Neither drug reverses or repairs the brain damage caused by the disease. Many Alzheimer’s experts, therefore, see them as just a first step in a potentially fruitful direction.

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

Three deaths were linked to donanemab in its clinical trial, the study says. Three participants in Leqembi’s trials also died, after suffering brain swelling and bleeding. But Eisai, the Japanese company that makes the drug alongside the Boston-based company Biogen, points out that it is unclear whether the drug contributed to these deaths because these patients already had complex medical problems.

The two drugs attack another protein, called amyloid, which builds up in plaques in the brains of Alzheimer’s patients. Through years of study, other anti-amyloid drugs failed to show that targeting amyloid could slow memory or thinking problems. And the FDA’s 2021 decision to give a kind of conditional approval to the anti-amyloid drug Aduhelm, while acknowledging uncertainty about its true benefits, has sparked controversy, congressional investigations and reluctance to prescribe it.

Donanemab and Leqembi, infusions given intravenously, are the first amyloid targeting 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 noticed by patients and families.

Leqembi patients, who received infusions every other week for 18 months, had a 27% slower decline than those who received placebo — a difference of less than half a point on an 18-point cognitive scale that assesses functions such as memory and problem resolution. problems. On the same scale in the donanemab study, the overall group of patients who received the drug, given as monthly infusions, declined 29% more slowly than the placebo group — or a difference of 0.7 points.

Some Alzheimer’s experts say that for the slowing of decline to be clinically significant or noticeable, the difference between a drug and a placebo must be at least 1 point.

Other aspects of the donanemab study should be especially intriguing to those skilled in the disease. Patients stopped receiving the drug and started taking a placebo if the amyloid was eliminated below a certain threshold. About half reached the threshold within a year, and their decline continued to slow even after they stopped taking the drug.

Lilly scientists estimated that it would take nearly four years for amyloid levels to break through the threshold again. It is uncertain whether the deceleration of decline would continue as amyloid begins to accumulate again.

The difficulty of predicting whether these medications will be meaningful in daily life is reflected in a patient’s experience in another study with donanemab.

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

In November 2021, Jim, a former electrician for a power company, began receiving monthly infusions of donanemab in a study comparing whether the drug clears more amyloid than the drug Aduhelm. His wife, a former high school math teacher, claims that the donanemab cleared the plaques and that the treatment was stopped after about 13 months. But the couple points out that they don’t know if the drug slowed his cognitive decline.

While her husband’s symptoms haven’t significantly worsened, says Sue Sirois, “there were some things he did without difficulty last summer that became a problem this summer.”

Jim is now unable to plug in the pool vacuum or cord the lawn mower. “He just struggles a lot with planning and anything that has multiple steps,” she says.

Even bowling, an activity in which he excelled, was affected. His aim can be less targeted now, and while he’s recently had a perfect game, “his average is probably about 20 pins lower than it used to be,” says Sue.

“I don’t know if the drug helped him or not,” he says. “I can’t say.”

But, she adds, “Whatever we can do to slow the progression or at least have some hope in that regard is what I would like to do.”

Translated by Luiz Roberto M. Gonçalves