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). He explained that this was a randomised, open-label, parallel-group, phase 3 trial in 31 centres across the USA [1]. Participants were 50–85 years old with early symptomatic AD. They were stratified on APOE ε4 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; 74 were assigned to each group. For aducanumab, US-approved label dosing was used; for donanemab, the following clinical trial protocol was used: 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 18 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, versus 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). Danunemab was also superior in reducing plasma P-tau217.

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

 

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

 

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Posted on 2 May, 202314 May, 2023