OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Lecanemab – Leqembi®

DRUG CLASS

Alzheimer Disease Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 10 February 2023

Abbreviations: ARIA-E, amyloid related imaging abnormalities with edema, effusions or microhemorrhage.

• Roberson ED. Alzheimer Disease. Treatment of central nervous system degenerative disorders. In, Brunton LL, Hilal-Danan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 333-5.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2023/761269Orig1s000MedR.pdf.

  (Multidisciplinary FDA review of lecanemab in support of its approval for use in Alzheimer disease in the US with discussion of safety mentions that the laboratory findings from the prelicensure studies did not reveal a “safety signal for hepatic related events”).
• Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8:595–608. [PMC free article: PMC4888851] [PubMed: 27025652]

  (Analysis of the role of amyloid-β in the etiology of Alzheimer disease supported by findings that the dominant mutations in amyloid precursor protein [APP] or the protease that metabolizes presenilin and generates amyloid-β are associated with early onset dementia, suggesting that imbalance of generation and clearance of amyloid-β is the early and perhaps initiating factor in Alzheimer disease and that monoclonal antibody therapy by increasing clearance might help correct the dyshomeostasis).
• Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016;537:50–6. [PubMed: 27582220]

  (Among 165 patients with early Alzheimer disease treated with 1 of 4 doses of aducanumab [1, 3, 6, or 10 mg/kg] or placebo monthly for one year, those treated with the higher doses showed evidence of decrease in brain amyloid-β accumulation and a trend for clinical improvement, but also higher rates of vasogenic edema [37% to 40%] compared with placebo [5%]; ALT elevations arose in 4 of 125 [3.2%] on aducanumab vs none of 40 on placebo).
• Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, et al. Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody. Alzheimers Res Ther. 2016;8:14. [PMC free article: PMC4822297] [PubMed: 27048170]

  (Among 60 patients with mild or moderate Alzheimer disease treated with one of 4 different doses of lecanemab or placebo for 12 months, treatment emergent adverse events were mild or moderate and similar to placebo with no symptomatic episodes of ARIA and the incidence of “out-of-range values in…clinical chemistry…parameters was comparable between different doses …and placebo”).
• Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13:80. [PMC free article: PMC8053280] [PubMed: 33865446]

  (Among 854 adults with early Alzheimer disease treated with one of 5 dose regimens of lecanemab or placebo for 18 months, a dose of 10 mg/kg given intravenously every 2 weeks yielded the optimal results in decreasing the decline in cognitive impairment and in decreasing amyloid beta burden with only mild-to-moderate adverse events including infusion related reactions in 20% [vs 3% with placebo], ARIA-E in 10% [vs 0.8% with placebo] and with “no relative changes between lecanemab and placebo in labs”).
• The Lancet. Lecanemab for Alzheimer's disease: tempering hype and hope. Lancet. 2022;400(10367):1899. [PubMed: 36463893]

  (Editorial on the status of lecanemab therapy for Alzheimer disease stresses the promise of the evolving studies, but that the difference of 0.45 point [of a total of 18 points] in the progression of cognitive decline between lecanemab and placebo therapy is of unclear clinical significance and long term studies will be needed to establish the its role in management of Alzheimer disease).
• van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388:9–21. [PubMed: 36449413]

  (Among 1795 adults with early Alzheimer disease treated with lecanemab or placebo intravenously every two weeks for 18 months, there was less progression of cognitive decline and greater reduction in brain amyloid burden with lecanemab therapy, which was associated with a slightly higher total [89% vs 82%] and serious adverse events [14% vs 11%], most commonly infusion related reactions [26% vs 7%], ARIA-E [12.6% vs 1.7%], headache [11% vs 8%] and falls 10.4% vs 8.1%]; no mention of ALT elevations or hepatotoxicity).