An experimental drug being tested against Alzheimer’s disease shows promise for slowing cognitive decline if used in the early stages, according to a new study in the New England Journal of Medicine. But some patients may experience dangerous side effects, including brain bleed.
“Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function,” researchers wrote in the study.
But they added that “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.”
Alzheimer’s is the most common form of dementia, believed to impact about 6.5 million older adults in the United States, according to the Alzheimer’s Association. The disease is marked by a decline in thinking, memory and language skills severe enough to interfere with daily life.
The experimental drug, lecanemab, is made by Eisai and Biogen, which presented the findings Tuesday at the Clinical Trials on Alzheimer’s Disease conference in San Francisco.
In the clinical trial, about 1 in 8 of those taking the drug, lecanemab, experienced some brain swelling, which Reuters noted has been seen in similar drugs. And 1 in 7 of those in the clinical trial had small brain bleeds — “a symptom linked to two recent deaths of people receiving lecanemab in a follow-on study — and five patients suffered macrohemorrhages.”
The company had reported in September that the trial, which involved 1,800 people with early-stage Alzheimer's, showed the experimental drug reduced cognitive decline by 27% on a clinical dementia scale, compared to those who were receiving a placebo.
Per Reuters, “Two deaths — both from brain hemorrhages — have been reported among participants in a trial extension. They involved a 65-year-old woman who received a type of medicine known as tissue plasminogen activator to clear blood clots after suffering a stroke and an 87-year-old who was on the blood thinner Eliquis.”
Eisai said those deaths “cannot be attributed to lecanemab.”
As CNBC reported, “Eisai said in a statement on Monday that all available safety information indicates lecanemab therapy is not associated with an increased risk of death overall, and added that it could not provide any information about specific patients ‘to protect the privacy of patients.’”
Study construct
Of the 1,795 volunteers with early-stage Alzheimer’s in the study, half received infusions every two weeks while the others were given a placebo.
Per CNBC, “Crucially, the drug removed enough amyloid protein that patients wouldn’t have had enough evidence of Alzheimer’s disease to qualify for entry to the trial.”
According to Dr. Ronald Petersen, from the Mayo Clinic, “All of these amyloid-lowering drugs carry a risk for increased brain hemorrhage. I think the primary outcomes, the secondary outcomes, the amyloid lowering is pretty impressive.”
Researchers said that at 18 months, nearly 7 in 10 trial participants who received the study drug had clearance of the sticky beta amyloid protein plaques that many researchers deem crucial to development of Alzheimer’s disease.
Fast track it?
The Alzheimer’s Association is urging the U.S. regulators to back the application for accelerated approval of lecanemab.
Other groups are also hailing the findings. CNBC quoted Dr. Susan Kohlhass, director of research for Alzheimer’s Research UK: “These exciting findings represent a major step forward for dementia research and could herald a new era for people with Alzheimer’s disease. This is the first time a drug has been shown to both reduce the disease in the brain and slow memory decline in clinical trials.”
But she, too, noted the need to be sure of the safety profile of lecanemab. “Lecanemab was associated with severe side effects, and it will be important for regulators to understand the safety profile of the drug before it is given a full license for use,” she said.
The FDA has previously approved Alzheimer’s drugs that show little improvement in cognition or ability to slow the neurocognitive decline that marks the disease.
But not everyone appeared to benefit in the trial. “The full data showed that some patients with a genetic risk of developing the mind-wasting disease did not benefit from lecanemab” based on the cognitive decline measure, Reuters reported. “They did, however, show improvement for the trial’s secondary goals, including other measures of cognition and daily function. Overall, lecanemab patients benefited by 23% to 37% compared with a placebo on these secondary trial goals.”
The U.S. Food and Drug Administration is expected to decide by Jan. 6 whether the drug should be approved under its accelerated review program. And either way, the company has said it will file for standard FDA approval for lecanemab in the U.S., while also seeking approval in Europe and Japan.