7/11/24 update: I do not recommend amyloid beta antibodies because effect size is tiny and they accelerate brain volume loss.
Drug: Lecanemab (LEQEMBI)
Pronunciation: le CAHN ue mab / leh KEM bee
Mnemonic: “Lickin’ β”
Mechanism: Monoclonal antibody against amyloid β (beta) peptides
Approved for: Mild Alzheimer's disease
Date of accelerated approval: 1/6/2023
Annual cost: $26,500
On January 6, 2023 lecanemab (Leqembi) received accelerated approval for treatment of Alzheimer’s disease (AD), specifically for mild cognitive impairment or mild dementia.
Lecanemab is the second monoclonal antibody approved for AD, following aducanumab (Aduhelm). Unlike aducanumab, lecanemab demonstrated actual clinical benefit in addition to simply reducing buildup of amyloid β in the brain. “Lecanemab licked aducanumab”. In clinical trials, lecanemab slowed AD decline by 27% percent over 18 months relative to placebo.
Refer to the aducanumab monograph for more information on the mechanism, risks, and side effects of amyloid β-clearing monoclonal antibodies. See also donanemab (Kisunla).
Lecanemab appears to be much safer than aducanumab in terms of brain edema and micro-hemorrhage. Amyloid-Related Imaging Abnormalities (ARIA) were less commonly seen with lecanemab (21% vs 9% placebo) than with aducanumab (41% vs 10% placebo). Incidence of symptomatic ARIA with lecanemab was only 2.3%, compared to 26% with aducanumab.
15% of subjects (vs 6% placebo) stopped lecanemab due to an adverse reaction. The most common side effect leading to discontinuation of lecanemab was infusion-related reaction. The overall incidence of infusion-related reactions was 20% with lecanemab (vs 3% placebo), which was much more commonly reported than with aducanumab. If infusion-related reactions occur with lecanemab, consider pre-medication with antihistamines, NSAIDs, or corticosteroids.
Although not directly compared, “lecanemab licked aducanumab” in most every category except for infusion-related reactions. However, three specific side effects reported with lecanemab but not with aducanumab (versus placebo) were cough 9% (vs 5%), atrial fibrillation 4% (vs 1%), and decreased lymphocyte count 4% (vs 1%).
High vigilance for Amyloid Related Imaging Abnormalities (ARIA) is necessary during the first 14 weeks of treatment with lecanemab. Risk of ARIA was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers. Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate treatment.
Interactions: Monoclonal antibodies are not subject to pharmacokinetic interactions. They are degraded into small peptides and amino acids in the same manner as endogenous IgG antibodies.
Dosing: 10 mg/kg intravenous infusion over 1 hour every 2 weeks. Before starting lecanemab confirm the presence of amyloid beta pathology and obtain a brain MRI (within one year) to evaluate for pre-existing Amyloid Related Imaging Abnormalities (ARIA). Obtain an MRI prior to the 5th, 7th, and 14th infusions. If radiographically observed ARIA occurs, treatment recommendations are based on type, severity, and presence of symptoms. Lecanemab may be continued based on clinical judgement if severity of ARIA-E (E for edema) on MRI is mild and symptoms are mild, but otherwise dosing should be suspended. Lecanemab may only be continued in ARIA-H (H for hemosiderin deposits) if mild on MRI and asymptomatic.
See also: aducanumab monograph
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