“It’s very exciting because this is the first treatment in our history that shows an unequivocal slowing of decline in Alzheimer’s disease,” said Dr. Christopher van Dyck, director of Yale’s Alzheimer’s Disease Research Unit, after the FDA approved lecanemab. The drug is sold as Leqembi and made by Eisai in partnership with Biogen. Van Dyck led the paper on its Phase 3 trial in The New England Journal of Medicine, and he is a paid consultant for Eisai, which funded the trials.
What the trial found
The study, called Clarity AD, enrolled 1,795 people with early-stage, symptomatic Alzheimer’s. After 18 months, those given lecanemab had declined 27 percent more slowly than those on a placebo. Imaging showed a significant drop in amyloid, the sticky protein the drug is built to clear, usually down to normal levels by the end of the trial. Decline slowed 26 percent on a key secondary measure of cognition and 37 percent on a measure of daily living.
When Biogen first announced the results, the Alzheimer’s Association called them “the most encouraging results in clinical trials treating the underlying causes of Alzheimer’s to date.” Dr. Susan Kohlhaas of Alzheimer’s Research UK called it a historic moment, the first Phase 3 Alzheimer’s trial in a generation to slow decline. “If you intervene early you can make an impact on how people progress,” she said.
Not everyone was convinced. Some researchers called the measured benefit small. A neurobiologist at the University of Texas who doubts the amyloid hypothesis told Nature that amyloid is “associated with the problem, but it isn’t ‘the’ problem.”
Van Dyck answered that directly. “Would I like the numbers to be higher? Of course, but I don’t think this is a small effect,” he said. He added that the data hint at larger gains with longer treatment, though more studies are needed to confirm it.
Safety and the black box warning
The FDA gave the drug accelerated approval in January 2023, based on amyloid clearance, and later granted full approval, the first full approval for an Alzheimer’s drug in two decades. It carries a black box warning, the agency’s strongest caution, because of safety concerns.
The most common side effect was an infusion-related reaction, in 26.4 percent of participants against 7.4 percent on placebo. Flushing, chills, fever, rash and body aches were typical. Most of these reactions (96 percent) were mild to moderate, and 75 percent came after the first dose.
Brain imaging also turned up abnormalities. Fluid formation, or edema, appeared in 12.6 percent of participants versus 1.7 percent on placebo. Small bleeds showed up in 17.3 percent versus 9 percent. Van Dyck said the edema is usually silent and is picked up on MRI, and dosing is paused only if symptoms appear. Most bleeds are microhemorrhages measured in millimeters, he said, and a catastrophic bleed is quite rare. He put the edema rate at roughly a third of that seen with aducanumab in published trials.
The label warns of brain swelling and bleeding, notes that people carrying a gene mutation that raises Alzheimer’s risk face a higher chance of swelling, and cautions against blood thinners.
Cost and access
The drug is given by intravenous infusion every two weeks. Eisai set the price at $26,500 a year, and supply was reportedly tight while full approval was pending. Medicare has said it will cover 80 percent of the cost. Yale is also running the AHEAD study, funded by the National Institutes of Health and Eisai, which tests lecanemab in people as young as 55 who have no symptoms yet but high amyloid levels.
Anyone weighing treatment should talk with their doctor.
Sources
- New Alzheimer’s Drug Slows Mental Decline By 27% in Trial Hailed as ‘Most Encouraging to Date’
- Lecanemab, the New Alzheimer’s Treatment: 3 Things To Know
