Substantial Doubt Remains about the Efficacy of Anti-Amyloid Antibodies

J Alzheimers Dis. 2024;97(2):567-572. doi: 10.3233/JAD-231198.

Abstract

With the FDA approval of aducanumab and lecanemab, and with the recent statistically significant phase 3 clinical trial for donanemab, there is growing enthusiasm for anti-amyloid antibodies in the treatment of Alzheimer's disease. Here, we discuss three substantial limitations regarding recent anti-amyloid clinical trials: 1) there is little evidence that amyloid reduction correlates with clinical outcome, 2) the reported efficacy of anti-amyloid therapies may be explained by functional unblinding, and 3) donanemab had no effect on tau burden in its phase 3 trial. Taken together, these observations call into question the efficacy of anti-amyloid therapies.

Keywords: Alzheimer’s disease; amyloid; clinical trials; tau.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Amyloidogenic Proteins*
  • Antibodies, Monoclonal, Humanized*
  • Emotions
  • Humans

Substances

  • donanemab
  • Amyloidogenic Proteins
  • Antibodies, Monoclonal, Humanized