A treatment that improves Alzheimer’s disease would be a great advance, but Leqembi (lecanemab), which recently received accelerated approval from the FDA, is not that drug. Yes, lecanemab slows decline to an extent detectable on a test, but not to an extent that a relative or caretaker would notice. This drug doesn’t actually make anything better. It just slows the rate that someone goes downhill over 18 months — by less than half a point on an 18 point scale. And we don’t know whether things get better or worse after that.
Leqembi is similar to Aduhelm (aducanumab), approved last year by the FDA, despite its advisory committee soundly rejecting it. Leqembi is slightly more effective — although it had no significant effect in women, those under age 65 and people who have two copies of APOE4, a gene variant that increased Alzheimer’s risk. Both Aduhelm and Leqembi cause brain bleeds, which can be fatal.
Leqembi and Aduhelm destroy amyloid plaque, a kind of protein that patients with Alzheimer’s have more of in their brains. It’s not clear whether amyloid causes Alzheimer’s, because many patients with brains full of amyloid have no symptoms of dementia. Amyloid may be a harmless marker of disease — or may even be a protective effort by the body to repair damaged cells. In any case, amyloid can fuse to blood vessel walls, and when the amyloid is attacked by a drug, the blood vessels in the brain may leak, sometimes catastrophically. Small bleeds are common; Aduhelm caused brain bleeding or swelling in 40% of patients; Leqembi is slightly less harmful, at about 21.5%, but that’s still one out of five patients.
