Yale researcher discusses the recent FDA approval of a new Alzheimer's disease treatment.
The Food and Drug Administration (FDA) recently granted accelerated approval to a new Alzheimer’s treatment called lecanemab, which has been shown to moderately slow cognitive and functional decline in early-stage cases of the disease.
Alzheimer’s disease is a progressive disorder that damages and destroys nerve cells in the brain. Over time, the disease leads to a gradual loss of cognitive functions, including the ability to remember, reason, use language, and recognize familiar places. It can also cause a range of behavioral changes.
The FDA’s decision followed results of a Phase III clinical trial published in the Jan. 5 issue of The New England Journal of Medicine. Christopher van Dyck, MD, director of Yale’s Alzheimer’s Disease Research Unit, was the lead author of the paper. (Dr. van Dyck is also a paid consultant for the pharmaceutical company Eisai, which funded the trials.)
Sold under the brand name Leqembi™ and made by Eisai in partnership with Biogen Inc., the drug is delivered by an intravenous infusion every two weeks.
The FDA’s accelerated pathway allows for earlier approval of drugs that treat serious conditions for which other treatments aren’t available or may no longer be effective. Eisai has also filed for traditional FDA approval.
Lecanemab works by removing a sticky protein from the brain that is believed to cause Alzheimer’s disease to advance.
“It’s very exciting because this is the first treatment in our history that shows an unequivocal slowing of decline in Alzheimer’s disease,” says Dr. van Dyck.
We talked more with Dr. van Dyck, who answered three questions about the new treatment.
How effective is lecanemab for Alzheimer’s disease?
In a trial that involved 1,795 participants with early-stage, symptomatic Alzheimer’s, lecanemab slowed clinical decline by 27% after 18 months of treatment compared with those who received a placebo.
“The antibody treatment selectively targets the forms of amyloid protein that are thought to be the most toxic to brain cells,” says Dr. van Dyck.
Study participants who received the treatment had a significant reduction in amyloid burden in imaging tests, usually reaching normal levels by the end of the trial. Participants also showed a 26% slowing of decline in a key secondary measure of cognitive function and a 37% slowing of decline in a measure of daily living compared to the placebo group.
“Would I like the numbers to be higher? Of course, but I don’t think this is a small effect,” says Dr. van Dyck. “These results could also indicate a starting point for bigger effects. The data appear encouraging that the longer the treatment period, the better the effect. But we’ll need more studies to determine if that’s true.”
They also beg the question about still-earlier intervention, adds Dr. van Dyck. Lecanemab is already being tested in the global AHEAD study for individuals who are still cognitively normal but at high risk of symptoms due to elevated levels of brain amyloid.
Yale currently has the largest number of participants in the AHEAD study, which is funded by that National Institutes of Health (NIH) and Eisai, and is enrolling participants as young as 55. “We may see a larger benefit if we intervene before significant brain damage has occurred,” he says.
Is lecanemab safe?
The most common side effect (26.4% of participants vs. 7.4% in the placebo group) of the treatment is an infusion-related reaction, which may include transient symptoms, such as flushing, chills, fever, rash, and body aches. The majority (96%) of these reactions were mild to moderate, and 75% happened after the first dose.
“We can medicate those individuals in advance if we find they have those side effects repeatedly,” says Dr. van Dyck. “We can use medications such as diphenhydramine, acetaminophen, Benadryl, or Tylenol. But this is generally not an issue.”
Another potential side effect associated with Lecanemab was amyloid-related imaging abnormalities with edema, or fluid formation on the brain. This occurred in 12.6% of trial participants compared to 1.7% in the placebo group. “It’s usually asymptomatic when it occurs, but we can detect it on MRI scans. We often don’t stop dosing if we see it, unless there are symptoms, in which case we would pause infusions until it fully resolves,” Dr. van Dyck says.
It’s important to note that the studies with lecanemab show substantially lower rates of this side effect than do published trials of other, similar drugs such as aducanumab—they're at about a third of the rate, explains Dr. van Dyck. “So, for drugs in this class, I think lecanemab has a favorable safety profile,” he says.
Lastly, 17.3% of trial participants experienced amyloid-related imaging abnormalities with brain bleeding compared to 9% in the placebo group.
“Most of the time we're really talking about microhemorrhages that are in the order of millimeters,” says Dr. van Dyck. “People with Alzheimer's disease are more prone to these events because of the amyloid deposits in their blood vessels, but a catastrophic bleed is quite rare.”
The medication’s label includes warnings about brain swelling and bleeding and that people with a gene mutation that increases their risk of Alzheimer’s disease are at greater risk of brain swelling on the treatment. The label also cautions against taking blood thinners while on the medication.
When will lecanemab be available for Alzheimer’s disease treatment?
While lecanemab may be offered in doctors’ offices soon, the price tag, which Eisai reportedly has set at $26,500 per year, may make it unaffordable for most people. Access will likely depend on whether the drug receives traditional FDA approval and whether Medicare will cover the drug, which is unknown at this point.