Lecanemab, an experimental drug for Alzheimer's, shows promise in slowing the progression of the disease but raises safety concerns over severe adverse effects in the clinical trial.
The drug's developers, pharmaceutical firm Eisai and biotechnology firm Biogen, announced in September that lecanemab slowed cognitive decline by 27% compared to a placebo in the 18-month-long study.
Lecanemab is a monoclonal antibody therapy that works by binding amyloid-beta peptides. When a person has Alzheimer's, abnormal levels of this naturally occurring protein clump together in the brain to form plaques that collect neurons and disrupt cell function.
A Phase 3 clinical trial, findings of which were published in the New England Journal of Medicine, included 1,795 participants 50 to 90 years of age with early Alzheimer's disease.
Half of the participants (898) received intravenous lecanemab (10 mg per kilogram of body weight every two weeks), and 897 received a placebo for 18 months.
At the beginning of the study, the participants' CDR-SB score, or the clinical dementia rating, was 3.2 in both groups. This 5-point scale is used to characterize six domains of cognitive and functional performance applicable to Alzheimer's disease: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
By 18 months, the CDR-SB score increased by 1.21 points in the lecanemab group, compared with 1.66 in the placebo group.
The participants' average amyloid level in the lecanemab group dropped from 77.92 centiloids to 55.48 centiloids, while in the placebo group, it increased by 3.64 centiloids.
The Alzheimer's Association welcomed the Phase 3 clinical trial results and called for the US Food and Drug Administration's (FDA) accelerated approval of lecanemab.
Concerns over adverse events
In the trial, severe adverse events were experienced by 14.0% of participants in the lecanemab group and 11.3% of participants in the placebo group.
Due to the adverse events, 6.9% and 2.9% of participants in the lecanemab and placebo groups, respectively, withdrew from the study.
The most common adverse effects included infusion reactions, which were largely mild-to-moderate, small hemorrhages on the brain, brain swelling, and headache.
Two participants died in the trial, but the drug developers say the deaths were not related to lecanemab.
"Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease," the study authors concluded.