A new drug called lecanemab is less controversial.It won’t reverse or stop Alzheimer’s disease, but Biogen And its Japanese co-developer, Eisai, Recently, an 18-month study of people in the early stages of dementia found that this treatment slowed cognitive decline by 27%. The two companies also collaborated on Aduhelm, but this time Eisai is leading the FDA response to lecanemab.
Despite lecanemab’s relatively modest benefits, many neurologists have hailed lecanemab as one of the greatest advances in the treatment of Alzheimer’s disease in nearly 20 years, and perhaps never before. . Experts hope the drug has reached a tipping point, with lecanemab given before symptoms develop or combined with other treatments to further delay or even prevent the disease. .
“This is the first time I’m convinced that a drug designed to slow down Alzheimer’s disease actually does that.”
Despite gaining FDA approval, Aduhelm has been snubbed by the health system and insurance companies amid safety concerns and criticism. The price tag first, and the heated debate about whether the drug slows the progression of dementia. The controversy culminated last spring when Biogen’s beleaguered chief executive resigned after Medicare announced it would not cover the drug for most patients.
Lecanemab has some challenges Similar concerns.
At least three deaths have been linked to the drug in recent months, according to media reports. Scientists are struggling to work out what slowing her disease progression by 27% would mean for the patient and her family. And unless an earlier Medicare ruling is overturned, lecanemab won’t be available for most people until regulators conduct a more thorough review of the drug.
Dr. Sam Gandy, an Alzheimer’s expert and professor of neurology and psychiatry at Mount Sinai Health System in New York, chose not to administer Aduhelm to his patients.
“It will certainly be discussed, but I don’t think it will end up significantly reducing approval,” he said of the commission’s report. “I think lecanemab deserves to be treated differently.”
Preliminary results from the trial, which included about 1,800 people with mild cognitive impairment or mild Alzheimer’s disease, were announced in late September and detailed in late November. To the relief of many scientists, these detailed results came as little surprise and helped confirm that the drug’s effects were real.
“It was really exciting to see the data in action,” he said.
Those who received lecanemab were 0.45 points better than those who received placebo on an 18-point scale measuring cognitive decline. Eisai estimates that with a modest effect he could slow the progression of the disease by 7.5 months, and that if a patient takes the drug for several years, he could possibly slow it four to five times longer. .
But experts say patients and their families may not immediately notice the difference.
said Brian Silver, Ph.D., associate director of neurology clinical operations at UMass Memorial Medical Center.
Lecanemab is the latest in a number of drugs designed to clear the brain of a sticky protein called amyloid-beta, whose buildup has been linked to Alzheimer’s disease. Scientists say similar drugs may have failed as they were tested in people with moderate or advanced disease if they cleared too little and too late of amyloid.
Dr. Reisa Sperling, director of the Alzheimer’s Research and Treatment Center at Brigham and Women’s Hospital, said: She believes that even the lecanemab study wasn’t treating patients early enough, “but I feel we’re on the right track.”
Sperling is leading a large clinical trial sponsored by Biogen, Eisai, and the National Institutes of Health that will test lecanemab in patients who have not yet shown signs of dementia but who have evidence of amyloid accumulation on brain scans. is testing. Early treatment is expected to further delay or prevent Alzheimer’s disease, and the results of the trial, which will follow the patient for her four years, are expected in 2027.
Another study, led by researchers at Washington University in St. Louis, combined lecanemab with an experimental treatment for Alzheimer’s disease to remove another problematic protein called tau, which is also implicated in Alzheimer’s disease.
“The goal here is to try to treat people before they get sick,” said Randall J. Bateman, PhD, a neurologist at the University of Washington who led the study. “Once symptoms appear, I don’t think just removing the amyloid will cure it.”
Just as oncologists combine different drugs to create patient-specific cancer-targeted therapies, experts say the future of Alzheimer’s disease treatment lies in amyloid-disrupting drugs like lecanemab and tau. We anticipate that it will be combined with other, still experimental, medications that eliminate or attenuate inflammation in the brain.
Diane Bovenkamp, principal scientist at the BrightFocus Foundation, a nonprofit that funds Alzheimer’s research, said:
But safety concerns about amyloid-lowering drugs may overshadow such ambitions.Both Aduhelm and lecanemab caused potentially dangerous brain hemorrhages and swelling in some recipients. . The incidence was lower with lecanemab, but scientists expect debate over whether lecanemab is safe enough.
Some neurologists, including VA’s Budson, believe the drug’s side effects can be managed in most patients, but the risks need to be better understood. Budson also noted that brain swelling and bleeding are more common in people who have two copies of her gene, called APOE4, which increases the likelihood of developing Alzheimer’s disease.
“I think I would have a different conversation with them,” he said.
Access to lecanemab may be initially restricted as debates about its safety evolve. Accelerated approval by the FDA was based on its ability to clear amyloid from the brain. After Aduhelm received similar approval in 2021, the Centers for Medicare and Medicaid Services would only allow such drugs after the FDA gave them full approval based on evidence that they actually helped slow the progression of the disease. He said he would pay for the amyloid-disrupting drug.
Eisai plans to complete the application for full approval early this year, but it could take the better part of a year for the FDA to make a decision.
Advocacy groups, including the Alzheimer’s Association, renewed their protests against the CMS decision in light of the positive data for lecanemab. The organization estimates that more than 2,000 people progress from mild dementia (which lecanemab is designed to treat) to more advanced disease each day.
“Current CMS policies that severely limit access to these treatments are eliminating options for people and leaving them vulnerable to irreversible diseases,” said Alzheimer’s Association president and incoming CEO Joanne Pike. continue to progress and widen health inequalities.
Ivan Cheung, chairman and CEO of Eisai’s U.S. business, recently told Globe that Eisai has been in talks with CMS for months and that advanced clinical trial data will persuade CMS to reconsider its decision. said he hopes
Another controversial issue surrounding the drug may be its yet-to-be-disclosed price. Cheung said Eisai plans to “provide a detailed explanation” about the price of lecanemab after it is approved.
Last month, Boston’s drug-price watchdog, the Institute for Clinical and Economic Review, released a draft 184-page report concluding that lecanemab could be cost-effective if priced between $8,500 and $20,600 per year. Did.
That range is higher than the $2,500 to $8,300 price tag Aduhelm calls “just right,” but well below the original $56,000 price tag for the drug, which Biogen later halved to $28,000.
Analysts estimate that lecanemab will generate $8 billion in annual sales, with profits split between Biogen and Eisai. Shares of both companies have risen about 40% and 60%, respectively, since positive data for lecanemab were first published in late September.
Globe staff Jonathan Saltzman contributed to this report.
Ryan Cross can be reached at ryan.cross@globe.com. follow him on twitter @RLCscienceboss.
