Donanemab shows rapid and deep plaque clearance in early Alzheimer’s Disease

More patients with early symptomatic Alzheimer’s Disease (AD) reached amyloid clearance and plaque reductions at 6 months with donanemab than with aducanumab in the TRAILBLAZER-ALZ 4 study. Donanemab's rapid and deep plaque clearance was associated with improvements in plasma phospho-tau, a key biomarker of AD.

TRAILBLAZER-ALZ 4 (NCT05108922) is the first study to directly compare disease-modifying therapies in patients with early AD, said Prof. Stephen Salloway (Warren Alpert Medical School of Brown University, RI, USA) [1]. The phase 3 trial was a randomised, open-label, parallel-group study performed in 31 centres across the USA. Participants were 50–85 years old with early symptomatic AD. They were stratified on APOEε4 status and amyloid burden at baseline. Participants randomised to donanemab could discontinue treatment on meeting predefined brain amyloid clearance criteria.

After 7 weeks of screening, 148 participants were included and 74 were assigned to each group. For aducanumab, US-approved label dosing was used; for donanemab, the following clinical trial protocol was applied: 3 doses of IV 700 mg donanemab every 4 weeks, followed by 1400 mg every 4 weeks. The co-primary endpoint was amyloid clearance (to <24.1 cl) at 6 months in the full-analysis set and in the intermediate tau-subpopulation.

Upon assessing florbetapir (18F) PET scans at 6 months, the researchers found that 37.9% of participants in the donanemab group met the co-primary endpoint in the full-analysis set, compared with 1.6% in the aducanumab group (P<0.001). In the intermediate tau subpopulation, these percentages were 38.5 and 3.8, respectively (P=0.008). Donanemab was also superior in reducing plasma phosphor-tau (P-tau217).

The safety profiles of both treatments were consistent with previous study data. “Despite the greater clearance of amyloid in the donanemab group, there was no difference in the incidence of amyloid-related imaging abnormalities (ARIA) characterised by either oedema and effusion (ARIA-E) or cerebral micro-haemorrhages (ARIA-H),” finished Prof. Salloway. The TRAILBLAZER-ALZ 4 study is ongoing; analyses at 12 and 18 months are underway.

1. Salloway SP, et al. Direct comparison of donanemab to aducanumab on amyloid lowering in early, symptomatic AD: TRAILBLAZER-ALZ 4 topline study results. S26.009, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June, 202325 March, 2024