Clear evidence this week that Eisai and Biogen’s drug lecanemab slows cognitive decline in early stage dementia has galvanized efforts among Alzheimer’s researchers toward a tantalizing goal - preventing dementia even before symptoms start.

Lecanemab is an antibody that targets and removes toxic clumps of a protein called amyloid beta that accumulate in the brains of patients with Alzheimer’s. Results from the companies’ 1,800-patient trial released on Tuesday showed convincingly that doing so also slows the advance of the mind-robbing disease.

In volunteers with mild cognitive impairment and early stage dementia, the drug showed a 27% reduction in cognitive decline after 18 months compared with those who got a placebo.

That amounts to an extra six months or so in which they can cook a meal, use a computer or pay their bills, said Dr. Christopher Van Dyck, director of the Alzheimer’s Disease Research Unit at Yale School of Medicine.

Scientists have already begun to debate whether the benefit is robust enough. But to many Alzheimer’s researchers, the findings suggest that preventing decline altogether is possible.

“It begs the question, what happens if you intervene when only minimal brain damage has been done?” Van Dyck said.

Work toward answering that question is underway in a trial called AHEAD, a public-private partnership with Eisai, Biogen, the National Institutes of Health and the US Alzheimer’s Clinical Trial Consortium. The global trial, taking place at 100 sites, is testing Eisai’s lecanemab in people who have elevated brain amyloid but are still cognitively normal.

“Suddenly, the relevance of the AHEAD study is really, really strengthened by these results,” Van Dyck said.

The findings were especially poignant for Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s and Massachusetts General hospitals in Boston, who leads the trial.

Sperling and colleagues selected lecanemab in 2019 based in part on the drug’s safety profile and its ability to remove amyloid from the brain as shown in an earlier midstage trial. At that time, the drug’s efficacy was less clear.

“I’ve been kind of holding my breath for the last two and a half years ... so it was thrilling to see these results,” she said.

Sperling said she is aware of the debate over whether the 27% benefit is meaningful enough for those with early stage disease, but for people who have yet to develop symptoms, that reduction would be game changing.

“If we saw that same slowing at the preclinical stage of Alzheimer’s disease, most people wouldn’t develop dementia in their lifetime - or at least a substantial proportion would not,” she said.

The AHEAD study, which in July 2020 started enrolling 1,400 healthy adults aged 55 to 80, involves two sister trials, divided according to how much amyloid is present in the brain. Those with lower amounts of amyloid will receive less frequent treatment, while those with more elevated levels will be dosed more frequently.

Initially, volunteers are screened for the presence of amyloid with a blood test from C2N Diagnostics, a St. Louis-based specialty diagnostics company. Those who test positive then undergo a special brain imaging test to confirm the presence of amyloid.

Using this screening test has already reduced by half the number of costly imaging tests, Sperling said.

She and colleagues also are considering adding a screening blood test looking for abnormal forms of another Alzheimer’s-linked protein called tau.—Reuters


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