Alzheimer’s disease experts are throwing their support behind the drug lecanemab, despite reports of two deaths tied to the experimental monoclonal antibody medication.
Following Tuesday’s publication in the New England Journal of Medicine of promising phase 3 clinical trial results, the Alzheimer’s Association said that the Food and Drug Administration should approve lecanemab on an accelerated basis because it could “meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”
The Alzheimer’s Drug Discovery Foundation similarly called the phase 3 trial results for lecanemab “an exciting milestone for the potential treatment of Alzheimer’s — the first step in our multi-pronged approach to treating this disease.” And USAgainstAlzheimer’s called the results “incredibly exciting news,” saying that the study “gives hope to the Alzheimer’s community.”
Results from the phase 3 CLARITY AD trial suggested that lecanemab “modestly” relieved cognitive impairment in people living with early Alzheimer’s disease. But the trial showed that adverse events, including brain swelling and bleeding in the brain, were common.
The journal Science reported this week that a 65-year-old woman who was taking the drug as part of a clinical trial died from a massive brain hemorrhage that some researchers linked to the drug. It was the second death linked to bleeding in the brain during the lecanemab trials. A physician who performed an autopsy on the patient attributed the death to the drug.
The FDA is expected to decide whether to approve the drug by Jan. 6.
Brain hemorrhage also is a concern when using aducanumab (Aduhelm), the first drug approved to treat Alzheimer’s by targeting anti-amyloid brain plaques. Use of the drug requires regular brain scans to watch for signs of bleeding or swelling in the brain. The Centers for Medicare & Medicaid Services has restricted the drug’s use to clinical trials only.
Treatment shows value
Despite those reports, the Alzheimer’s Association, which also supports aducanumab, said that the results show that lecanemab will provide individuals more time to participate in daily life and live independently, and it called on CMS to cover the drug if approved by the FDA.
“Treatments that deliver tangible benefits to those living with mild cognitive impairment due to Alzheimer’s and early Alzheimer’s dementia are as valuable as treatments that extend the lives of those with other terminal diseases,” the association stated.
UsAgainstAlzheimer’s co-founder and Chair George Vradenburg noted that lecanemab works differently than most treatments currently in the pipeline, which attack amyloid in the brain.
“It is our hope the Food and Drug Administration and the Centers for Medicare & Medicaid Services keep that in mind as they evaluate whether to approve this drug and determine whether Medicare will cover it,” he said in a statement, adding that “patients deserve nothing less than to have confidence that the approval process is fair and free from bias.”
Howard Fillit, MD, co-founder and chief science officer of the ADDF, said that although media reports have called attention to safety concerns, the data show that lecanemab was generally well-tolerated. He added that Alzheimer’s is a complex disease with multiple underlying causes, requiring a combination drug approach.
“We are closer than ever to developing a new generation of drugs that targets the many causes of this devastating disease,” Fillit said in a statement. “We have a lot of ground to cover to reach our goal of slowing cognitive decline by 100%, but we are on our way.”
Fallout follows media coverage
After the FDA approved aducanumab, a group of neuroscientists from the University of California, Irvine, discovered a “surprising impact” on attitudes about research into Alzheimer’s disease.
A panel of outside experts had advised the FDA against approval of the drug, saying that its ability to decrease plaques hadn’t shown an effect on disease progression. Media coverage was widespread on the agency’s controversial accelerated approval of the first Alzheimer’s drug in almost 20 years.
Researchers at the UCI Institute for Memory Impairment and Neurological Disorders found that news coverage of the decision actually made individuals less willing to volunteer for pharmaceutical trials of Alzheimer’s medications. Their study results were published last week in the Journal of Alzheimer’s Disease,
The UCI researchers asked people aged 50 to 79 who had expressed willingness to take part in drug research whether they would be interested in enrolling in a hypothetical four-year study of a plaque-reducing monoclonal antibody and a plaque-preventing drug. The study was conducted eight days after the FDA gave aducanumab the green light.
“We found those who had heard about the FDA decision before our follow up became less willing to take part in a drug trial,” Marina Ritchie, a neurobiology and behavior graduate student and corresponding author, said in a statement. “The people who learned about it from our materials demonstrated absolutely no change in their willingness.”
UCI MIND Director Joshua Grill, PhD, said in a statement that the findings were surprising, as they went against previous data showing that people generally are more willing to participate in studies involving approved drugs compared with investigational ones.
“We believe it could be evidence of the powerful influence of media coverage of science,” Grill said.
The study authors said that their findings may offer important insights for Alzheimer’s disease researchers.
“Alzheimer’s is the most important medical condition society faces, and we need an army of citizen volunteers to participate in drug trials,” Grill said. “Anything that diminishes credibility in scientific research impedes our progress. Media coverage has the potential to influence people’s choices. That can hold us back or push us forward.”
The UCI MIND team plans further research, with an emphasis on how to better ensure the participation of diverse populations in Alzheimer’s clinical trials.
In another study, the results of which were published in October in the Journal of Prevention of Alzheimer’s Disease, 56% of the 1,028 respondents aged 50 to 64 said they were not likely to take part in a trial of a dementia-prevention drug. The greatest percentage of survey respondents, 39%, said they did not want to be “guinea pigs,” 23% said they thought that dementia would not affect them, 22% said they were afraid of being harmed by the research, 15% were concerned that participation would take too much time and 5% reported a fear of learning information about themselves. The researchers did not see any differences across age, sex, and racial and ethnic groups.