On 13 March, Dr. Mark Mintun, Dr. Daniel Skovronsky and co-Investigators published topline results of the TRAILBLAZER-ALZ clinical trial, which was designed to evaluate the efficacy of the anti-amyloid antibody, donanemab. These results were presented at the 2021 AD/PD conference, and published simultaneously in the New England Journal of Medicine (NEJM).
TRAILBLAZER-ALZ was a Phase 2, multi-center, randomised and placebo-controlled clinical trial of donanemab in people with early, symptomatic Alzheimer's disease (AD). TRAILBLAZER-ALZ, which was sponsored by Eli Lilly, enrolled 257 participants aged between 60 and 85, 131 of whom were assigned to receive donanemab. Donanemab is an antibody that specifically targets a form of modified amyloid protein that is present in established amyloid plaques in the brains of people with AD. Over the course of 72 weeks, participants received a monthly intravenous infusion of donanemab or placebo, undergoing regular clinical evaluations that included MRI and PET scans, neuropsychological tests, biomarker measurements and other assessments.
Encouragingly, analysis of the TRAILBLAZER-ALZ results revealed that participants receiving donanemab showed slower cognitive and functional decline, as measured using the iADRS scale (an average difference of 3.2 points compared to placebo). In objective terms, authors of the study suggested that this was equivalent to 25% slower disease progression in the donanemab group. However, no significant differences in secondary outcome (e.g. CDR-SB and MMSE scales) were observed. Similar to clinical trials of other anti-amyloid antibodies, TRAILBLAZER-ALZ revealed a substantial reduction in brain amyloid load over 76 weeks, as measured using amyloid-PET scans. Over 26% of participants receiving donanemab also showed signs of ARIA-E, a measure of fluid accumulation in the brain observed via MRI. A follow-on trial, TRAILBLAZER-ALZ2, is currently enrolling participants to study the safety and efficacy of donanemab over a longer period of time, with an estimated completion date in March 2023.
https://www.nejm.org/doi/full/10.1056/NEJMoa2100708?query=featured_home
