Schiffer, a 59-year-old fashion historian in North Berwick, Maine, has no symptoms of Alzheimer’s disease. But in 2021, her family history prompted her to apply to join a clinical trial testing a drug in people at high risk. To participate, volunteers cannot have cognitive impairment. But they needed to test positive for a biomarker that puts them at greater risk for mental decline — deposits of a toxic, sticky protein in the brain called beta-amyloid that is the hallmark of the disease.
Shafer had a PET scan of her brain and it tested positive for amyloid. Finding out she was eligible for the study, she said, “was both the best and the worst day.”
Since February 2022, Schaefer has driven about 160 miles round trip every two weeks to Brigham and Women’s Hospital, where researchers are testing an intravenous drug they hope will prevent, or at least delay, symptoms. It is one of about 100 clinical trial sites around the world participating in the study, which will eventually recruit 1,400 volunteers between the ages of 55 and 80.
The drug in question, Leqembi, was developed by Cambridge-based Biogen and its Japanese commercial partner Eisai. In a historic decision issued on July 6, the Food and Drug Administration approved this drug for people who already show early symptoms of Alzheimer’s disease, a scourge that affects more than 6 million Americans. Priced at $26,500 per year per patient, Leqembi was the first drug proven effective in slowing the rate of cognitive decline in people with mild symptoms of Alzheimer’s disease. It is thought to be done by removing amyloid plaques from the brain.
The approval has strengthened families affected by Alzheimer’s disease and the doctors who treat them. However, the slowing of the disease in those with early symptoms was relatively modest — 27% during a separate 18-month study conducted by the companies — and the treatment did not come without potentially serious side effects.
Schaffer was enrolled in a different study to determine whether Leqembi would produce more dramatic benefits for people who had not yet shown signs of cognitive decline and memory loss. those signs Experts say the disease may not appear for 10 to 20 years after deposits of amyloid and other toxic proteins form in the brain.
“I often use the cholesterol analogy,” said Dr. Risa Sperling, a neurologist at Harvard and Brigham Medical School and the lead researcher on the study funded by EISA and the National Institute on Aging. “If you give someone a statin while they’re in the ICU, it won’t do anything. But when you give statins before someone has a heart attack or stroke, it actually changes the morbidity and mortality rates. Alzheimer’s is very similar. If we can follow This essential process is early enough that we can one day prevent dementia.
To qualify for the four-year prevention study, called AHEAD, Schaefer had to undergo a series of cognitive tests to make sure she was healthy. Tasks included counting backwards by 7 out of 100, listening to a story and telling as many details as possible, and remembering pictures of household items that I had reviewed in a file. She was relieved to learn she did not have cognitive impairment, but was understandably dismayed when she later tested positive for amyloid.
So far, she has received nearly 50 intravenous injections in her arm at the hospital’s Alzheimer’s Research and Treatment Center. Each infusion takes about an hour. She spends the time playing video games on her mobile phone, including Sudoku. She plans to receive the injections in Boston for another two and a half years.
Neither she nor the trial investigators know whether Schaeffer was taking Lekembe or a saline placebo. But she suspects she is getting the drug because she had a mild allergic reaction after her first injection. Regardless, Schaefer said her motivation for volunteering wasn’t necessarily to help herself.
“Whether I personally benefit from it or not is beside the point,” said Schafer, who showed framed photos of relatives who died of Alzheimer’s disease to a Globe photographer during a recent infusion. “I’ve watched the people I love go through this, and I know what it’s like for them when they’re gone…”. Her voice receded. “I do my best in difficult situations when I feel like I’m doing something,” she said.
Sperling said the researchers plan to run positron emission tomography (PET) scans halfway through the four-year injection period, and then again after the trial ends, to see if the participants’ amyloid deposits have grown. Sperling said investigators also perform periodic cognitive tests and check on trial participants and their relatives or friends to see if they notice any mental decline, such as difficulty following news stories or handling finances.
Volunteers in the prevention study began receiving the shots in late 2020. The trial, which is still enrolling participants, is scheduled to be completed by 2027, Sperling said.
If alchemy prevents symptoms after four years, it remains to be seen whether recipients will need to continue taking the drug, Sperling said. However, the researchers lower the dose in the middle of the study period.
It’s not the only large clinical trial testing the amyloid-clearing drug in people without Alzheimer’s symptoms.
About two years ago, pharmaceutical giant Eli Lilly began recruiting volunteers to study a similar experimental drug called dunanimab. This amyloid-scraping drug generated even more impressive results than Lekembe’s in a recently published study of patients with early Alzheimer’s symptoms. Dunanimab slowed the rate of cognitive decline by about 35 percent. Based on that data, donanimab is widely expected to win FDA approval this year for people with mild disabilities.
As in Eisai’s prevention study, Lilly is testing donanemab separately in volunteers who do not have symptoms but are at risk for developing them because of evidence of amyloid deposits. Ultimately, the trial is expected to include 3,300 volunteers at dozens of sites in the United States and Japan.
Chris Tuala, a 69-year-old author of historical romances who lives in suburban Phoenix, didn’t need a little convincing to volunteer in Lilly’s study, called TRAILBLAZER, at the nearby Banner Alzheimer’s Institute.
Her paternal grandmother and father both had dementia, and her father’s brother was diagnosed with Alzheimer’s when he was just 60 years old.
“Maybe the thought of losing myself, of losing my mind, is the only thing I worry about in my life,” she said. My prayer for the past ten years has probably been, “Please, God, don’t take my mind.”
Twala has so far received four batches of donanimab. And unlike the likembe infusion, which is given every two weeks, the donanimab infusion is given monthly, and trial participants only get nine. Tuala doesn’t know if she’s getting the drug or a placebo either, but she thinks she might be getting donanimab because she felt dizzy after the first two doses.
As in the Lugambi trial, volunteers who received a placebo will later be randomly offered the drug if it is proven to be safe and effective.
While the history of Alzheimer’s drug trials is riddled with notable failures, Don Brooks, global disease development lead for Lilly, said offering donanimab to people at high risk before symptoms appear makes sense.
Lilly’s study of 1,736 patients, published in July in the Journal of the American Medical Association, found that dunanimab slowed the progression of early Alzheimer’s disease in patients who started receiving the drug when they had less of another protein called tau that forms tangles in cells. brain.
“We saw the strongest efficacy in the least advanced patients,” she said. “It’s all about slowing down and, ideally, preventing the onset of what we know is a debilitating and often fatal disease.”
Dr. Paul Eisen, MD, who directs the Alzheimer’s Treatment Research Institute at the University of Southern California’s Keck School of Medicine, agrees.
“We used to say that Alzheimer’s disease lasts about seven years from the onset of dementia to death,” said Eisen, who is helping run the Lekembe trial with Sperling. “But this is the end of what we now consider a 25-year process that begins with amyloid buildup.”
“It’s intuitively clear that the earlier you start (treatment) the better,” he said. “Why not attack pathology when the brain is functioning normally?”
Jonathan Saltzman can be reached at email@example.com.