The plaque comes out; most of the disease stays. Alzheimer's brains build up sticky amyloid-beta plaque; these lab-built antibodies flag it for clean-up. It works well: a year of donanemab clears about 84% of plaque, and half of patients go plaque-free and stop 1. But by the time plaque shows on a scan, a second protein called tau is already killing neurons and inflammation is set. So decline slows only about a quarter; it does not reverse.
The numbers. In early-stage trials, lecanemab slowed decline 27% over eighteen months 2; donanemab ran 22% slower overall, 35% slower in low-tau patients, and cut the risk of reaching the next disease stage by 39% 1. Why experts split: that difference is half the size a patient would notice, and pooling the whole drug class finds a smaller average 3. Europe saw the same data and refused donanemab on benefit-versus-risk grounds 4.
Almost nobody qualifies, and this is a neurologist's decision. Bring these questions:
What the win looks like. Over eighteen months, the average treated patient stays themselves about five months longer: the morning routine holds a few more weeks, the grandkids' names take a moment longer to slip, the driver's-licence conversation gets pushed to the next family meeting. Whether the lines keep separating after that is unknown, because the trial's comparison groups are gone 8.
The real cost is money and time. List price is $26,500 a year for lecanemab, about $32,000 for a donanemab course; with scans and workup, year-one cost passes $40,000 9. Medicare covers both if the clinic reports to a registry, but a typical patient still pays around $5,300 in coinsurance. On lecanemab, patient and caregiver visit an infusion centre 26 times a year; that load often decides the call.
The fine print — when to skip it, and what people get wrong
When to skip. Hard stops: more than four old microbleeds or a larger bleed on baseline MRI, surface iron staining, warfarin or a direct blood thinner, or amyloid angiopathy with a prior bleed 6. Unstudied in moderate or severe disease.
What headlines get wrong. It does not reverse or cure Alzheimer's; patients still decline, just slower. It works only for confirmed early Alzheimer's, not other dementias. The brain swelling is not merely a scan number: some patients are hospitalised and a few have died 1.
- 1Sims JR, et al. (2023). Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. link
- 2van Dyck CH, et al. (2023). Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. link
- 3Alves F, et al. (2023). Anti-amyloid therapies do not slow Alzheimer's disease progression: a systematic review and meta-analysis. Brain Communications. link
- 4EMA (2025). Refusal of the marketing authorisation for Kisunla (donanemab). link
- 5Wang Z, et al. (2025). Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction (TRAILBLAZER-ALZ 6). Alzheimer's & Dementia. link
- 6Cummings J, et al. (2023). Lecanemab: Appropriate Use Recommendations. Journal of Prevention of Alzheimer's Disease. link
- 7Reish NJ, et al. (2023). Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke. New England Journal of Medicine. link
- 8Petersen RC, et al. (2023). Expectations and Clinical Meaningfulness of Randomized Controlled Trials. Alzheimer's & Dementia. link
- 9CMS (2023). Statement: Broader Medicare Coverage of Leqembi Available Following FDA Traditional Approval. link
დაკავშირებული სახელმძღვანელოში (5)
- — Before reaching for an expensive, risky drug, clear out the everyday meds quietly fogging the same brain.
- — Your APOE status shapes both eligibility and the brain-bleed risk of these drugs — test before deciding.
- — Slows decline sounds big until you read the actual size — about five months over eighteen.
- — The shingles shot appears to cut dementia risk about a fifth — the same disease these drugs treat once it has already taken hold.
- — A specific stage of Alzheimer's is one of the narrow places high-dose vitamin E has supervised evidence.
Anti-Amyloid Drugs for Alzheimer's
Two large phase 3 RCTs with biomarker-confirmed populations (van Dyck 2023, Sims 2023) meeting primary endpoints, FDA traditional approval for both lecanemab (2023) and donanemab (2024). Mechanism (amyloid clearance) directly validated by PET imaging. Falls short of 5 because clinical-meaningfulness debate and EMA-FDA regulatory divergence reflect genuine uncertainty about effect size.
Modest disease-modification in early AD: 22–35% slowing on iADRS/CDR-SB in CLARITY-AD (van Dyck 2023) and TRAILBLAZER-ALZ 2 (Sims 2023), with 39% reduction in progression to next clinical stage on donanemab. Effect on all-cause mortality unproven and confounded by ARIA-attributable deaths in trials.
Functional/cognitive trajectory in early-AD patients slowed by ~5 absolute months over 18 months on the CDR-SB scale (van Dyck 2023). Real but small effect; below commonly-cited 1-point MCID and Alves 2023 meta-analysis pools the class effect at −0.24 CDR-SB points, below MCID thresholds.
Lecanemab: 26 biweekly IV infusions/year plus 4–5 monitoring MRIs in first 14 months; donanemab: monthly infusions for ~12 months. Diagnostic pre-work (amyloid PET or LP, APOE, baseline MRI) typically 6–12 weeks. Cumulative time burden 60–80 hours/year plus transport — substantial caregiver load for the typical 70-year-old patient.
Indirect: preservation of functional independence may sustain mood/wellbeing in patients and reduce caregiver distress, but no direct mood endpoint in CLARITY-AD or TRAILBLAZER-ALZ 2. Counterweighted by anxiety from ARIA monitoring and infusion-schedule stress.
Lecanemab list $26,500/year; donanemab ~$32,000/course; plus amyloid PET, APOE genotyping, serial MRIs, and infusion-centre fees push first-year burden above $40,000. Even with Medicare Part B coverage, typical out-of-pocket is ~$5,300/year before supplemental (CMS 2023). NICE rejected lecanemab as not cost-effective.