OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Aducanumab – Aduhelm®

DRUG CLASS

Alzheimer Disease Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 25 June 2021

• 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/2021/Aducanumab​_BLA761178_Dunn_2021_06_07.pdf.

  (Multidisciplinary FDA review of aducanumab 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 identify any clinically meaningful change in patients treated with aducanumab”).
• Ratner M. Biogen's early Alzheimer's data raise hopes, some eyebrows. Nat Biotechnol. 2015;33:438. [PubMed: 25965736]

  (News report on release of interim results of a phase 1 study of aducanumab in Alzheimer disease which described decreases in β-amyloid plaques in treated patients as assessed by PET scan, but with no data on clinical efficacy in reversing or slowing progression of dementia; the results were encouraging enough directly go to phase 3 trials of the monoclonal antibody).
• 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).
• Ferrero J, Williams L, Stella H, Leitermann K, Mikulskis A, O'Gorman J, Sevigny J. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2016;2:169–76. [PMC free article: PMC5651340] [PubMed: 29067304]

  (Phase one study of escalating single doses of aducanumab [0.3, 1, 3 10, 20, 30 and 60 mg/kg] vs placebo in 53 patients with mild-to-moderate Alzheimer disease; four receiving the 60 mg/kg dose developed symptomatic amyloid related imaging abnormalities; no mention of ALT elevations or hepatotoxicity).
• 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).
• Hawkes N. Merck ends trial of potential Alzheimer's drug verubecestat. BMJ. 2017;356:j845. [PubMed: 28202490]

  (News report on the termination of a large randomized controlled trial of verubecestat [a small molecule inhibitor of β site amyloid precursor protein cleaving enzyme 1: BACE-1] because of futility).
• Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement. 2021;17:696–701. [PubMed: 33135381]

  (In a reanalysis of results from two large controlled trials of aducanumab in early Alzheimer disease, the authors conclude that there was likely a dose related effect on brain amyloid-β plaque accumulation, but the studies did not show evidence of clinical benefit, which calls for a third, adequately powered trial using higher doses and in more extended populations of subjects with Alzheimer disease).
• Alexander GC, Emerson S, Kesselheim AS. Evaluation of aducanumab for Alzheimer disease: scientific evidence and regulatory review involving efficacy, safety, and futility. JAMA. 2021;325:1717–8. [PubMed: 33783469]

  (Summary of the conclusions of the FDA advisory committee on aducanumab which were based upon results of two phase III randomized controlled trials in early Alzheimer disease patients, both of which were terminated early after interim analyses indicated futility; but on post-hoc reanalysis, statistically significant benefit was found with the higher dose in one of the 2 trials; because of discrepancies in outcomes in the two trials and only slight clinical benefit achieved in one arm of the 2 studies, the committee recommended that aducanumab not be approved until another trial confirms the efficacy and safety of the high dose regimen).