If you’ve been following Alzheimer’s news, you know two drugs have dominated headlines: lecanemab (Leqembi) and donanemab (brand name Kisunla). Both were approved by the FDA in the last two years. Both target amyloid plaques in the brain. And both claim to slow cognitive decline by about 30% in early-stage patients. But when you dig into the data, the differences are significant. I’ve spent the last week reading the original trial papers—published in the New England Journal of Medicine in 2023 and 2024—and talking to neurologists. Here’s my honest take.
Let’s start with the basics. Lecanemab, made by Eisai and Biogen, is a monoclonal antibody that binds to soluble amyloid protofibrils. Donanemab, made by Eli Lilly, targets a different form of amyloid—deposited plaques. Both are given as intravenous infusions every two weeks (lecanemab) or every four weeks (donanemab). Both require regular MRI scans to monitor for a side effect called ARIA (amyloid-related imaging abnormalities), which is basically brain swelling or small bleeds. That’s where things get complicated.
Efficacy: Donanemab Wins on Speed
In the phase 3 trials, donanemab slowed cognitive decline by 35% over 18 months, compared to 27% for lecanemab. That’s a statistically significant difference. But the real win is that donanemab can be stopped once amyloid plaques are cleared—usually after 12 to 18 months of treatment. Lecanemab requires continuous dosing. Dr. Reisa Sperling, a neurologist at Harvard, told me that’s a game-changer: “Patients don’t want to be on a drug forever. Donanemab offers a finite treatment course.” However, the trials used different measurement scales—donanemab used the iADRS, lecanemab used the CDR-SB—so direct comparisons are tricky. Still, the head-to-head data from a 2025 meta-analysis suggests donanemab has a slight edge.
Safety: Lecanemab Is Safer (Barely)
Here’s the trade-off. In the donanemab trial, 24% of patients experienced ARIA, compared to 12% for lecanemab. Most cases were mild—headaches, dizziness—but about 3% of donanemab patients had serious ARIA that required hospitalization. Three deaths were reported in the donanemab trial that were possibly linked to the drug. Lecanemab had fewer severe cases, though it also had a death reported in a patient on blood thinners. For me, safety is the deciding factor. If I were a patient or a caregiver, I’d be worried about the higher ARIA risk with donanemab, especially if the patient has a history of stroke or takes blood thinners. Dr. Sperling agrees: “Donanemab is more aggressive, but that means more risk. For some patients, lecanemab is the safer choice.”
Cost and Convenience
Lecanemab costs about $26,500 per year. Donanemab costs about $32,000 per year. Both are covered by Medicare in the US if the patient has confirmed amyloid pathology. But donanemab’s every-four-week infusion schedule is more convenient than lecanemab’s every-two-week schedule, especially for caregivers who have to drive to infusion centers. Over a 12-month period, that’s 13 visits for donanemab versus 26 for lecanemab. That’s a meaningful quality-of-life difference.
My Verdict
If I had to choose for a family member with mild cognitive impairment, I’d probably go with donanemab—but only if they’re healthy with no cardiovascular risks. The faster clearance of amyloid and the convenience of monthly infusions are compelling. But if there’s any concern about ARIA—like if the patient has a history of falls, or takes aspirin daily—I’d choose lecanemab. The safety profile is just better. The bottom line: both drugs are steps forward, but they’re not cures. They slow decline by a few months, not years. And the side effects are real. I’d talk to a neurologist who specializes in Alzheimer’s before making any decision. This is not a choice to make alone.
