The drug, lecanemab, was associated with a dangerous type of brain swelling in nearly 13% of patients in the 18-month study involving nearly 1,800 participants with early-stage Alzheimer’s.
Some patients also experienced bleeding in the brain, with five patients experiencing macrobleeds and 14% experiencing microbleeds — a symptom linked to two deaths of people given the drug in a follow-up study.
The companies said in September that lecanemab — an antibody designed to remove sticky deposits of a protein called amyloid beta — reduced the rate of cognitive decline on a clinical dementia scale (CDR-SB) by 27% compared to a placebo.
“All of these amyloid-lowering drugs carry a risk for increased cerebral hemorrhage,” said Dr. Ronald Petersen of the Mayo Clinic in Rochester, Minnesota. “I think the primary outcomes, the secondary outcomes, the amyloid reduction are pretty impressive.”
The Alzheimer’s Association said the data confirms the drug “could meaningfully change the course of the disease,” and called on US regulators to approve the company’s application for accelerated approval.
Eisai shares were up 3.6% in Tokyo afternoon trading, while Biogen shares were up 0.9% in after-hours trading. They are up 60% and 47%, respectively, since the study’s initial findings were announced in late September.
The full data showed that some patients with a genetic risk of developing the mind-altering disease did not benefit from lecanemab based on the CDR-SB measure.
However, they did show improvement for the trial’s secondary goals, including other measures of cognition and daily functioning. Overall, lecanemab patients benefited from 23% to 37% compared to placebo on these secondary study goals
“I believe it’s an important benefit that warrants full approval. But of course we want a bigger benefit,” says Dr. Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California and co-author of the published study. in the New England Journal of Medicine.
He said lecanemab is likely to provide more benefit if it’s given earlier in the disease, “before you’ve built up enough irreversible damage to cause symptoms.”
Detailed data from the study were presented at the Clinical Trials on Alzheimer’s Disease meeting in San Francisco.
PROOF OF AMYLOID THEORY
Eisai believes the study results prove a long-held theory that removing beta-amyloid from the brains of people with early Alzheimer’s can slow the progression of the disease.
After 18 months, 68% of the trial participants treated with lecanemab had amyloid clearance, Eisai said. The drug also lowered levels of tau, another protein that forms toxic tangles in brain cells.
The two cerebral hemorrhage deaths reported in the follow-up study were a 65-year-old woman who was given a type of drug known as tissue plasminogen activator to clear blood clots after a stroke and an 87-year-old who was on the blood thinner Eliquis .
Eisai said it believes the deaths “cannot be attributed to lecanemab.”
The company has established protocols for monitoring brain swelling and sees no need for restrictions on which patients are eligible for lecanemab, Ivan Cheung, the US chairman of Eisai, told Reuters in an interview.
Dr. Howard Fillit, chief science officer at the Alzheimer’s Drug Discovery Foundation, said doctors always balance the benefits and risks of therapies. “Currently, I would be hesitant to give this drug to someone on blood thinners,” he said.
The U.S. Food and Drug Administration will decide on Jan. 6 whether to approve lecanemab under its “accelerated” review program, which requires evidence that a drug can affect a biomarker associated with a disease, such as a reduction in beta. amyloid in the brain.
Regardless of that decision, Cheung said Eisai plans to file for standard FDA approval of the drug soon and will also seek approval in Europe and Japan.