TY - JOUR
T1 - Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit
AU - Høilund-Carlsen, Poul F.
AU - Alavi, Abass
AU - Barrio, Jorge R.
AU - Castellani, Rudolph J.
AU - Costa, Tommaso
AU - Herrup, Karl
AU - Kepp, Kasper P.
AU - Neve, Rachael L.
AU - Perry, George
AU - Revheim, Mona Elisabeth
AU - Robakis, Nikolaos K.
AU - Sensi, Stefano L.
AU - Vissel, Bryce
N1 - Publisher Copyright:
© 2024
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Aducanumab
KW - Alzheimer's disease
KW - Amyloid-PET
KW - ARIA
KW - Brain volume
KW - Donanemab
KW - FDG-PET
KW - Lecanemab
U2 - 10.1016/j.arr.2024.102348
DO - 10.1016/j.arr.2024.102348
M3 - Review
C2 - 38830549
AN - SCOPUS:85197085056
SN - 1568-1637
VL - 99
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 102348
ER -