Topline results: Donanemab superior to aducanumab in early symptomatic Alzheimer’s disease
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BOSTON — More patients with early symptomatic Alzheimer’s disease reached amyloid clearance and plaque reductions at 6 months with donanemab vs. aducanumab, according to a presentation at the American Academy of Neurology annual meeting.
Stephen P. Salloway, MD, MS, the Martin M. Zucker Professor of Psychiatry and Human Behavior and professor of neurology at Brown University Warren Alpert Medical School, and colleagues conducted the phase 3, randomized TRAILBLAZER-ALZ-4 study to investigate amyloid-plaque clearance with donanemab (n = 71) vs. aducanumab (n = 69) in study participants with early symptomatic AD. Patients were stratified by Apolipoprotein E 4 at baseline, he said.
Researchers used the standard prescribing guidelines for aducanumab and the clinical trial protocol designed for donanemab, which entailed participants receiving three doses of IV 700 mg donanemab every 4 weeks then 1,400 mg in subsequent doses every 4 weeks.
“Donanemab showed substantial lowering of amyloid plaque compared to aducanumab,” Salloway said. “Thirty-eight percent of patients in the donanemab arm got below the cutoff for being amyloid positive at 24 weeks.”
Patients could discontinue treatment if the level got below the cutoff for AD, he noted.
When assessing florbetapir 18 PET scans at 6 months, researchers reported that 37.9% of patients in the donanemab-treated arm achieved amyloid clearance vs. 1.6% in the aducanumab-treated arm (P < .001). In the intermediate tau subpopulation, 38.5% of the donanemab-treated arm achieved amyloid clearance vs. 3.8% in the aducanumab-treated arm (P = .008).
“Interestingly, a number of studies have shown an effect of amyloid-lowering antibodies on plasma phospho-tau — either 217 or 181 — and this did as well,” Salloway said. “However, I think that there is a correlation between the degree of amyloid-lowering and the change in p-tau.”
Salloway also noted there was no difference in the amyloid-related imaging abnormalities rate between groups, despite greater amyloid-lowering in the donanemab arm.
More data from the ongoing trial will be available at 1 year and 18 months, he said.