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. 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.
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.
How Lecanemab works?
Lecanemab is a monoclonal antibody that targets amyloid,
a protein that forms sticky plaques in the brain and is a key characteristic of
Alzheimer’s disease. The drug binds to the amyloid protein, preventing it from
clumping together and forming plaques. It also promotes the clearance of
existing plaques, which may reduce inflammation and neuronal damage in the
brain.
Several trials of lecanemab have shown positive results
in reducing amyloid plaques in the brain. One study found that patients
receiving high doses of the drug had a 90% reduction in amyloid plaque levels
after 18 months of treatment, compared to placebo. Another study showed that patients
receiving lecanemab had a significant reduction in amyloid plaques after just 6
months of treatment. These findings suggest that lecanemab has the potential to
slow or even halt the progression of Alzheimer’s disease by reducing the amount
of amyloid in the brain.
In addition to reducing amyloid plaques, lecanemab may
also improve cognitive function in patients with Alzheimer’s disease. An
analysis of data from a phase 2 trial showed that patients receiving the drug
had better scores on cognitive tests than those receiving placebo, particularly
in tasks related to memory and language. These results suggest that lecanemab
may have a positive impact on cognitive function in patients with Alzheimer’s
disease.
One key concern in developing drugs for Alzheimer’s
disease is the risk of side effects. Previous drugs that targeted amyloid have
had limited success in clinical trials, in part because of side effects such as
swelling and bleeding in the brain. However, studies of lecanemab have reported
few adverse events, and the drug appears to be well-tolerated in patients. This
is an encouraging finding, as it suggests that lecanemab may be a safe and
effective option for treating Alzheimer’s disease without causing serious side
effects.
What were the results of the phase 3 clinical trial?
This is one of the largest clinical trials in Alzheimer's
disease and was unique in that it had higher participation of historically
underrepresented groups than in previous studies. It also allowed volunteers
with more medical comorbidities to enter the study. Usually, participant
populations in studies like these are healthy, so this created a more
representative sample of the Alzheimer's population in the real world.
The volunteers underwent a battery of tests that measured
cognitive performance, functional performance, and behavior, and brain imaging
and monitoring of biomarkers of the disease. The drug was associated with
extremely robust amyloid plaque clearance; most of the participants at 18
months had no detectable plaques in their brain. Other downstream effects
associated with Alzheimer’s, like tau and neuronal inflammation biomarkers,
also looked like they moved more towards normal.
There was a statistically significant separation between
participants who received the drug compared to those who received a
placebo on global measures of cognitive and functional impairment, keeping in
mind that participants in the study had a confirmed diagnosis of Alzheimer’s
but their cognitive symptoms were still very mild at the time of their
enrollment. This provides the first definitive evidence that clearing
amyloid beta improves cognitive performance. It is important to note that
both groups experienced cognitive decline over the 18 months of the study, but
the placebo group declined at a faster rate.
About 12.5 percent of participants showed evidence of
mild to moderate localized brain swelling, but this was not life threatening,
rarely clinically evident, and resolved over several weeks when the medication
was temporarily halted. We also saw a higher rate of micro hemorrhages, or
pinhead bleeds, that we often see in patients with Alzheimer's disease, so the
treatment requires careful clinical and MRI monitoring, particularly in the
first 6-12 months.
Who should take this drug?
The FDA prescribing information specifies that lecanemab
is appropriate for people with early Alzheimer's with confirmation of elevated
beta-amyloid. The treatment was studied in people living with early Alzheimer's
dementia and MCI due to Alzheimer's who showed evidence of a buildup of
beta-amyloid plaques in the brain. The therapy has not been tested on people
with more advanced stages of Alzheimer's or those without clinical symptoms.
How much will this drug cost?
In a news release, the manufacturers of lecanemab
announced they are setting the price of the drug at $26,500 a year.
How is this drug administered?
The treatment is administered through an IV every two
weeks, lasting 45 to 60 minutes for each infusion. Typically, infusions can be
done at hospitals and infusion therapy centers.
Sources and Additional Information:
https://www.yalemedicine.org/news/lecanemab-leqembi-new-alzheimers-drug
