Alzheimer's drug slowed cognitive decline overall in trial, but with major side effects for some

An experimental drug for Alzheimer's disease from Eisai and Biogen slowed cognitive decline in a closely watched trial, but may carry a risk of dangerous side effects for certain patients, according to new data presented on Tuesday.

The drug, lecanemab, was associated with a type of brain swelling in 12.6 per cent of trial patients, a side effect previously seen with similar drugs. Fourteen per cent of patients had microhemorrhages in the brain — a symptom linked to two recent deaths of people receiving lecanemab in a follow-on study — and five patients suffered macrohemorrhages.

The companies said in September that the 18-month trial, which enrolled nearly 1,800 participants with early-stage Alzheimer's, found that treatment with lecanemab reduced the rate of decline on a clinical dementia scale (CDR-SB) by 27 per cent compared to a placebo.

The results suggest lecanemab slowed the advance of Alzheimer's disease in its early stages by four to five months over the 18-month period of the study.

"All of these amyloid-lowering drugs carry a risk for increased brain hemorrhage," said Dr. Ronald Petersen of the Mayo Clinic in Rochester, Minn. "I think the primary outcomes, the secondary outcomes, the amyloid-lowering is pretty impressive."

The Alzheimer's Association said the data confirms the drug "can meaningfully change the course of the disease for people in the earliest stages of Alzheimer's disease," and called on U.S. regulators to approve the company's application for accelerated approval.

The trial showed no benefit on the CDR-SB measure for some patients with a genetic risk of developing the mind-wasting disease.

About 16 per cent of participants had two copies (homozygous) of the APOE4 gene variant known to raise the risk of developing Alzheimer's, 53 per cent had one copy of the gene (heterozygous) and 31 per cent were non-carriers.

"For that small group of homozygous patients, when it comes to CDR-SB, we don't see a signal favouring lecanemab," said Ivan Cheung, Eisai's U.S. chairman, in an interview. He suggested that could be because homozygous study patients who were given a placebo fared better than expected.

The APOE4 carriers did show improvement on the trial's secondary goals, including other measures of cognition and daily function. Overall, lecanemab patients benefited by 23 per cent to 37 per cent compared with a placebo on these secondary trial goals.

"I believe it's an important benefit that will justify full approval. But of course, we want a bigger benefit," said Dr. Paul Aisen, director of the University of Southern California Alzheimer's Therapeutic Research Institute and a co-author of the study published in the New England Journal of Medicine. He said lecanemab is likely to provide greater benefit if given earlier in the disease, "before you've accumulated enough irreversible damage to be causing symptoms."

Detailed data from the study were presented at the Clinical Trials on Alzheimer's Disease meeting in San Francisco.

Eisai, based out of Tokyo, believes the trial results prove a longstanding theory that removal of sticky deposits of a protein called amyloid beta from the brains of people with early Alzheimer's can delay its advance.

At 18 months, 68 per cent of trial participants treated with lecanemab had amyloid clearance, Eisai said.