How does lecanemab work? What promise does the therapy hold?
Dr. Honig: Lecanemab is a monoclonal antibody that binds amyloid and was designed to remove amyloid from the brain. It has long been suggested that removing the protein might slow the progression of Alzheimer’s disease.
In the clinical trial, the treatment was administered every two weeks by intravenous infusion. The trial results showed that it slowed decline for people with early Alzheimer’s disease by about 27% to 37%, depending on the clinical test measure. After 18 months of treatment, the mean amyloid level in most treated patients was below the threshold for amyloid positivity, meaning that a radiologist would not even know the patient had Alzheimer’s disease.
In preliminary results of a substudy on subcutaneous lecanemab, patients who received weekly injections of the therapy showed comparable amyloid plaque removal and similar side effects to those who got lecanemab intravenously biweekly.
Does lecanemab reverse problems linked to Alzheimer’s disease, its signs, and its symptoms? It does not. Does it slow them down? It does, by a variety of measures; one, by reducing amyloid levels. And this is the first medication clinically proven to do so.
Are there other Alzheimer’s treatments?
Donanemab is another drug of the same class. Like lecanemab, it removes beta amyloid and slows disease progression. Eli Lilly, its manufacturer, submitted to the FDA for full approval, and a decision is expected sometime around the end of 2023.
The FDA granted aducanumab, a similar treatment, accelerated approval in 2021 based on it demonstrating amyloid removal from the brain. But aducanumab did not have clear evidence of clinical efficacy in Alzheimer’s disease, such as proven slowing of the progression of cognitive decline, and this drug does not have full FDA approval at this time.
How many participants in the clinical trial of lecanemab experienced the associated risks, and what is there to know about these risks?
The main risks of amyloid-lowering medications include brain swelling (ARIA-E) and brain bleeding (called ARIA-H), which participants in both the main intravenous study and subcutaneous substudy experienced.
Almost 13% of participants who were on intravenous lecanemab experienced brain swelling. There were 3% that had what is called symptomatic brain swelling, which means that they had swelling of the brain that caused clinical signs or symptoms, and less than 1% had serious symptoms. The bleeding events in the brain, called “micro-bleeds,” are rather common in Alzheimer’s disease, and in the absence of the swelling there was no difference between rate of bleeding events in those on treatment and placebo. It is rare that patients have symptoms from a micro-bleed; it is noticed by the neurologists or radiologists looking at the scans.