Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit

Poul F. Høilund-Carlsen*, Abass Alavi, Jorge R. Barrio, Rudolph J. Castellani, Tommaso Costa, Karl Herrup, Kasper P. Kepp, Rachael L. Neve, George Perry, Mona Elisabeth Revheim, Nikolaos K. Robakis, Stefano L. Sensi, Bryce Vissel

*Corresponding author for this work

Research output: Contribution to journalReviewpeer-review

Abstract

Based on “reducing amyloid plaques in the brain”, the U.S. Food and Drug Administration has granted accelerated and full approval for two monoclonal anti-Alzheimer's antibodies, aducanumab and lecanemab, respectively. Approval of a third antibody, donanemab, is pending. Moreover, lecanemab and donanemab are claimed to cause delay in the cognitive decline that characterizes the disease. We believe that these findings are subject to misinterpretation and statistical bias. Donanemab is claimed to cause removal of up to 86 % of cerebral amyloid and 36 % delay in cognitive decline compared to placebo. In reality, these are very small changes on an absolute scale and arguably less than what can be achieved with cholinesterase inhibitor/memantine therapy. Moreover, the “removal” of amyloid, based on the reduced accumulation of amyloid-PET tracer, most likely also reflects therapy-related tissue damage. This would also correlate with the minimal clinical effect, the increased frequency of amyloid-related imaging abnormalities, and the accelerated loss of brain volume in treated compared to placebo patients observed with these antibodies. We recommend halting approvals of anti-AD antibodies until these issues are fully understood to ensure that antibody treatment does not cause more harm than benefit to patients.

Original languageEnglish
Article number102348
JournalAgeing Research Reviews
Volume99
Number of pages5
ISSN1568-1637
DOIs
Publication statusPublished - 2024

Keywords

  • Aducanumab
  • Alzheimer's disease
  • Amyloid-PET
  • ARIA
  • Brain volume
  • Donanemab
  • FDG-PET
  • Lecanemab

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