The monoclonal antibody Lecanemab (brand name Leqembi®) has shown compelling efficacy in slowing cognitive decline by approximately 50% in patients with early stage Alzheimer’s disease far exceeding earlier estimates. This milestone was revealed in a fresh four year analysis presented at the 2025 Alzheimer’s Association International Conference.(Reuters)
Trial Results: From 27% to 34 to 50% Slower Decline
In the Clarity AD Phase III study a global, randomized, placebo-controlled trial involving nearly 1,800 participants with mild cognitive impairment (MCI) or mild dementia Lecanemab demonstrated a 27% reduction in cognitive decline over 18 months, measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR SB).(Wikipedia)
Follow‑up data from an open label extension revealed sustained benefit over time. After four years, Lecanemab slowed clinical decline by 34% compared to expected progression in untreated cohorts noting relative improvement from baseline trajectories in ADNI and BioFINDER. In certain subgroups with low tau accumulation (early stage patients), delay in decline neared 50%, with more than half showing sustained cognitive/routine living benefits.(Globedge).
Clinical Significance: What Does 50% Slower Mean?
- The CDR SB instrument gauges functional and cognitive performance; lower numbers reflect less decline.
- Over 18 months, Lecanemab treated patients worsened by 1.21 points, versus 1.66 points on placebo a 0.45 point difference, or roughly 27% slower decline.(Wikipedia)
- In longer term follow up, the treated group’s trajectory diverged further: a decline of 1.75 fewer CDR SB points at four years compared to predicted natural history.(PR Newswire)
- In the subgroup with minimal tau build up, 56 to 69% maintained or improved baseline cognitive/daily function.(PR Newswire)
This suggests that initiating treatment early, when pathological hallmarks are emerging but symptoms remain mild, yields greater and more durable slowing of disease progression.
Benefits vs. Risks and Limitations
Efficacy caveats:
- Some experts describe the 0.45 point difference at 18 months as modest and possibly below perceptible threshold for patients.(PMC, icer.org)
- Effectiveness may vary by subgroup; for example, individuals carrying two ApoE ε4 alleles may derive less benefit and face higher safety risk.(Eisai)
- Earlier analyses flagged a 31% greater benefit in men versus women in Clarity AD data, highlighting uncertain consistency across sexes.(PMC)
Safety profile:
- Key risk is amyloid related imaging abnormalities (ARIA) transient brain swelling or micro bleeds. These peaked within first year and declined thereafter. Serious events were rare and mostly non fatal.(Eisai)
- Real world clinic data reported minimal hospitalization or discontinuation for ARIA within the first 9 months.(Neurology live)
Access & cost concerns:
- Lecanemab was fully approved by the U.S. FDA in July 2023, with earlier accelerated approval granted in January 2023.(Wikipedia)
- It recently gained EU approval (April 2025) for early-stage AD in patients with one or no ApoE ε4 copy, excluding homozygotes.(Eisai)
- Australia’s TGA declined registration as of March 2025.(Wikipedia)
- Pricing remains steep (~$30,000/year); health authorities have challenged its cost‑effectiveness given modest benefits.(icer.org, Wikipedia)
Summary Table
| Feature | Details |
|---|---|
| Primary Trial (18 mo) | ~27% slower cognitive decline (CDR SB endpoint) |
| Four-Year Outcome | ~34% slower decline overall; subgroups up to ~50%; benefits sustained |
| Key Subgroup Benefit | Tau‑low / early stage patients saw greatest delay and functional stability |
| Main Risk | ARIA: brain swelling/micro-bleeds, mostly in first treatment year |
| Regulatory Status | FDA approved (US), EU approved, not registered in Australia |
| Challenges | High cost, variable response by genetic profile, modest perceived benefits |
Looking Ahead
The latest four year analysis elevates Lecanemab from a modestly beneficial therapy to one with potentially transformative impact for early stage Alzheimer’s patients, particularly when initiated before substantial tau pathology.
Further avenues include:
- Evaluating injectable (subcutaneous) formulations expected for U.S. approval by late 2025 to ease infusion burdens.(Reuters)
- Broader real world follow up studies to validate efficacy across diverse populations.
- Research in pre symptomatic patients to assess whether early amyloid removal delays or prevents clinical onset.(WashU Medicine, Reuters)
Bottom line: While not a cure, Lecanemab offers a clinically meaningful slowing of Alzheimer’s progression, with around 50% reduction in cognitive deterioration for those treated early enough marking an important advance in disease modifying therapy.
