Lecanemab

Anti-amyloid beta (Aβ) monoclonal antibody, targets protofibrils

Lecanemab

Leqembi

Lecanemab (brand name Leqembi) is a humanized monoclonal antibody targeting soluble Aβ protofibrils, FDA-approved for Alzheimer disease (MCI/mild AD) via accelerated approval in January 2023 and converted to traditional approval in July 2023. Unlike aducanumab, lecanemab's pivotal trial (Clarity AD, 1795 patients, 18 months) was clearly positive: ~27% relative slowing of cognitive decline on CDR-SB.

The effect is real but modest, and comes with substantial cost (~$26,500/year), inconvenience (biweekly IV infusions), and ARIA risk (especially in APOE ε4 homozygotes, boxed warning recommends genotyping before treatment). Several deaths from ARIA-related cerebral edema/hemorrhage have been reported, particularly in patients on concurrent anticoagulants.

The broader question of whether lecanemab's modest clinical benefit justifies the cost, risk, and burden is actively debated. Reasonable observers disagree.

Experience

👥 No personal reports yet

⚕ No clinical reports yet

Log in to add your own experience.

Problems

No problems yet. Be the first to suggest one.

+ Add a problem

Titration strategies

No titration strategies yet. Be the first to suggest one.

+ Add a titration strategy

Effects

ARIA-E (vasogenic edema) and ARIA-H (microhemorrhages), both often asymptomatic but can be serious. Infusion reactions. Headache. Boxed warning: APOE ε4 homozygotes at higher ARIA risk (~33% vs ~13% in non-carriers); genotype testing recommended before initiating.

+ Add an effect

Pharmacodynamics

Humanized IgG1 with high affinity for Aβ protofibrils (and lower affinity for monomers and plaques). Promotes microglial Aβ clearance via Fc-receptor engagement.

Interactions

No interactions reported yet.

+ Add an interaction

Relevant anecdote

No anecdotes yet. Share a relevant one.

+ Add an anecdote

Relevant Literature

No literature entries yet.

Log in to submit relevant literature.

Summary

Classes

Anti-amyloid beta (Aβ) monoclonal antibody, targets protofibrils

Common uses

Alzheimer disease (MCI or mild dementia stage); FDA accelerated approval Jan 2023 → traditional approval July 2023

Pharmacy

Starting dose

10 mg/kg IV every 2 weeks

Preparations

200 mg/2 mL, 500 mg/5 mL vials for IV infusion

US FDA Max

10 mg/kg q2w

Pharmacology

Routes

IV infusion (60 min) every 2 weeks; outpatient or infusion-center setting

Onset

Slowing of cognitive decline over 18 months (modest effect, ~27% relative slowing)

Duration

Ongoing dosing

Half-life

~5-7 days

Bioavailability

100% (IV)

Pregnancy

Limited data

Legal status

Rx; REMS-like program for ARIA monitoring

Purported mechanism

Humanized IgG1 monoclonal antibody with higher affinity for soluble Aβ protofibrils than for monomeric Aβ or insoluble plaques. The protofibril-targeting rationale: soluble oligomers and protofibrils are hypothesized to be the most neurotoxic Aβ species. Promotes microglial clearance and reduces protofibril burden.