Lecanemab (Leqembi) granted FDA approval for treatment of early-stage Alzheimer’s disease

Two important things happened this week.  On the Fourth of July, my granddaughter Emily got her first ride in a canoe. She was thrilled. The other important thing that happened this week was the FDA approval yesterday of lecanemab (trade name Leqembi) for early-stage Alzheimer’s disease. The approval of lecanemab has been highly anticipated since the publication of a phase 3 clinical trial that showed a 27% decrease in cognitive decline in subjects with MCI or early dementia associated with Alzheimer’s disease. Experts have argued over whether this 27% slowing of cognitive deterioration would be noticed by the patient, but statistically it appears to be significant and real. This may be the first medication to show slowing of cognitive deterioration in Alzheimer’s disease.

The potential problem with lecanemab and other drugs in this class is that they can cause brain swelling and/or bleeding.  These side effects are called ARIA, amyloid-related imaging abnormalities. This is usually not a problem, and often they don’t even cause symptoms, but a small number of people using this drug have had severe reactions resulting in hospitalization and at least three deaths. People who have two copies of the APOE-4 allele, the most common genetic risk factor for Alzheimer’s disease, have a greater chance of getting ARIA, especially severe ARIA. Therefore, the FDA Prescribing Information for lecanemab contains a black box warning that recommends genetic screening before using this drug. APOE-4 carriers may still take the drug, but they need to know of their increased risk of adverse complications including death. For those who choose to receive the drug despite the added risk, increased surveillance with frequent MRI scans will be necessary.

Would I choose to take lecanemab knowing that I have two copies of the APOE-4 allele? No, because I have already had life-threatening side effects from taking another drug in this class, aducanumab. In my opinion, no one who has had severe ARIA in response to any of the anti-amyloid monoclonal antibodies should take lecanemab or other drugs of this class.