Drug Slows Alzheimer’s, But Can It Make a Real Difference?

An experimental Alzheimer’s drug has modestly slowed the inevitable worsening of the brain disease, researchers reported Tuesday — but it remains unclear how much it might do in people’s lives.

Japanese drugmaker Eisai and its American partner Biogen had announced earlier this fall that the drug lecanemab appeared to be working, a much-needed bright spot after repeated disappointments in the search for better Alzheimer’s treatments.

Now the companies are providing the full results of the study of nearly 1,800 people in the early stages of the mind-destroying disease. The data were presented at an Alzheimer’s meeting in San Francisco and published in The New England Journal of Medicine. US regulators could approve the drug as soon as January.

Every two weeks for 18 months, study participants received intravenous lecanemab or an inactive infusion. The researchers tracked them using an 18-point scale that measures cognitive and functional ability.

Those given lecanemab declined more slowly — a difference of less than half a point on this scale, the research team led by Dr. Christopher van Dyck of Yale University concluded.

That’s a hard change to understand, but measured in a different way, lecanemab delayed worsening in patients by about five months over the course of the study, Eisai’s Dr. Michael Irizarry told The Associated Press. Lecanemab recipients were also 31 percent less likely to progress to the next stage of the disease during the study.

“That translates to more time in the earlier stages,” when people are functioning better, Irizarry said.

But doctors are divided on how much of a difference these changes can make for patients and families.

“The small difference reported in this study is unlikely to be noticeable to individual patients,” said Dr. Madhav Thambisetty of the National Institute on Aging, who noted that he was not speaking for the government agency.

He said many researchers believe a significant improvement would require at least a full-point difference on that 18-point scale.

But Dr. Ron Petersen, an Alzheimer’s expert at the Mayo Clinic, said the drug’s effect was “modest, but I think it’s clinically significant” — because even a few months of delaying progression could provide someone a little more time when working independently.

The study is important because it shows that a drug that attacks a sticky protein called amyloid — thought to be one of several culprits behind Alzheimer’s — can delay the progression of the disease, said Maria Carrillo, chief scientific officer of the Alzheimer’s Association.

“We all understand that this is not a cure, and we’re all trying to really understand what slowing Alzheimer’s means, because this is a first,” Carrillo said.

But any delay in early cognitive decline could be significant for “how much time we have with loved ones at a stage of the disease where we can still enjoy family and trips, vacations, bucket lists,” she said.

Drugs that target amyloid can cause side effects that include swelling and bleeding in the brain, and lecanemab did, too. Some type of this swelling was seen in about 13% of recipients. Eisai said most were mild or asymptomatic.

Two deaths were also publicly reported among lecanemab users who were also taking blood-thinning drugs for other health problems. Eisai said Tuesday that the deaths could not be attributed to the Alzheimer’s drug.

But Mayo’s Petersen said that if lecanemab is approved for use in the U.S., he would avoid prescribing it to people on anticoagulants at least initially.

And Thambisetty said the reports of deaths raise concerns about how the drug may be tolerated outside of research studies “where patients are likely to be sicker and have more other medical conditions.”

The Food and Drug Administration is considering approving lecanemab under its fast-track program, with a decision expected in early January. If approved, it would be the second anti-amyloid drug on the market.

Almost all treatments available to the 6 million Americans with Alzheimer’s — and millions more worldwide — only temporarily relieve symptoms. Scientists don’t yet know exactly how Alzheimer’s forms, but one theory is that the buildup of gunky amyloid plays a key role, though drug after drug targeting it has failed.

In a controversial move last year, the FDA approved the first amyloid-targeting drug, Biogen’s Aduhelm, despite a lack of evidence of better patient outcomes. Insurers and many doctors have been hesitant to prescribe the expensive drug — another reason experts have been eagerly awaiting information on how well the new lecanemab might work.

If the FDA approves lecanemab, patients and their families will need a voice in deciding whether it’s worth the battle of intravenous infusions and the risk of side effects for the chance of at least some delay in progression, Petersen said.

“I don’t think we’re going to stop the disease in its tracks” with drugs that target amyloid alone, he added, saying a combination of drugs that target additional Alzheimer’s culprits will be needed.

Researchers are preparing to test lecanemab with other experimental drugs and how it works in high-risk people before they show the first signs of memory problems.