Eisai Co. and partner Biogen Inc. said their drug significantly slowed Alzheimer’s disease, making it the first medicine to blunt progression of the most common dementia in a definitive, large-scale trial.
Lecanemab reduced the pace of cognitive decline in people with early disease by 27% over 18 months when compared with a placebo, meeting the main goal of the trial, the companies said in a statement. The benefit came with side effects, including brain swelling and bleeding, though severe cases were rare.
The result marks a major milestone for researchers who have been trying in vain for decades to stop the inexorable decline tied to the disease. How much of a difference it will make for patients and families is less clear. While it appears to unambiguously slow the disease, the medicine doesn’t restore mental capacity or totally stop its loss.
The consistent pattern of improvement “is what the field has hoped for, and should result in favorable regulatory actions,” said David Knopman, a clinical neurologist at the Mayo Clinic in Rochester, Minnesota.
“There is an important cautionary note however: the magnitude of the delay – which was a slowing of decline – was small,” he said. “We can only hope that the benefit is durable and could grow with time. Those long-term properties are unknowable at this time.”
Eisai was untraded at its upper limit in Tokyo as bids outweighed offers by more than 19 times. Eli Lilly & Co., which is developing a similar drug, rose 6.7% in the US in after hours trading Tuesday. Biogen’s shares were halted. The drug was originally licensed from BioArctic AB in Sweden.
The Alzheimer’s Association welcomed the results, saying they were the most encouraging findings to date from drugs aimed at treating the underlying causes of the disease. Lecanemab has the potential to change the course of the disease and help people in the earliest stages retain their abilities, remain independent and fully participate in daily life, the group said.
Pharmaceutical and biotechnology analysts were equally bullish.
“We finally have what we believe to be a clean win in Alzheimer’s disease,” Evan David Seigerman, an analyst at BMO Capital Markets, wrote in a note to clients. “The top-line data are clear to us — lecanemab slows the rate of cognitive decline.”
The trial met every goal that was set, including other measures of mental function and the ability to perform daily activities, the companies said.
Lecanemab is already being reviewed by US regulators under a special “accelerated approval” pathway. The companies said they would apply for full US approval by the end of March, which could eventually lead to broad coverage by the Medicare insurance program for the elderly. The companies plan to file in Europe and Japan at the same time.
There were some serious side effects. In the study involving 1,795 patients, 21.3% of those given the drug experienced brain swelling or brain bleeding, compared with 9.3% of those on a placebo. While most cases were asymptomatic, 2.8% of people on lecanemab had symptomatic brain swelling, the companies said.
Lecanemab is the latest in a long line of drugs designed to remove amyloid, a toxic protein that clutters the brain and is a hallmark of Alzheimer’s disease. Numerous previous trials of amyloid-lowering drugs have failed or produced mixed results.
The results bolster the amyloid hypothesis: a long-held but controversial theory that the buildup of amyloid over time is one of the main causes of the disease. The success is likely to raise hopes for other anti-amyloid drugs in development, including medicines in final-stage trials from Roche Holding AG and Eli Lilly.
The results “prove the amyloid hypothesis,” said Eisai Chief Executive Officer Haruo Naito in a statement.
The positive study isn’t the end of the challenges for Eisai and Biogen, who are collaborating on the drug that had some early controversy and will split the profits.
A previous medicine they developed together, called Aduhelm, was approved in the US in June 2021 despite contradictory trial results. While the amyloid-lowering antibody slowed the decline from Alzheimer’s modestly in one big trial, another showed no effect. Both were halted early. But the Medicare program for the elderly refused to pay for the drug that initially cost $56,000 a year outside of clinical trials, and it ended up a commercial failure.
Lecanemab is likely to receive full US Food and Drug Administration approval based on the study results, said Lon Schneider, professor of Psychiatry and Behavioral Sciences at University of Southern California. That’s not the end of the discussion, however.
“The debate is going to be about the small effect size” and whether it is clinically meaningful, Schneider said in an interview.
Other questions also remain, including reimbursement and potential rivals. The success will increase the confidence about the potential of competing candidates, which will complicate investors’ view on the commercial opportunity, Jefferies analyst Stephen Barker has said.
Roche said it was encouraged to learn of the first positive results from an amyloid-targeting study in the third and final phase of drug development. Data from its two pivotal studies on the Alzheimer’s drug gantenerumab will be available in the coming months, it said.
Eisai and Biogen didn’t release details of their study findings. The full results are expected to be published in a medical journal and presented at the Clinical Trials in Alzheimer’s Disease meeting in November. Roche’s gantenerumab studies are expected to be presented there, too.