More patients with early symptomatic AD achieved amyloid clearance and plaque reductions at 6 months with donanemab than with aducanumab in TRAILBLAZER-ALZ 4.
TRAILBLAZER-ALZ 4 is the first study to directly compare disease-modifying therapies in patients with early AD, according to Stephen Salloway, MD, MS. According to Dr. Salloway, the trial was a randomized, open-label, parallel-group, phase 3 trial conducted at 31 centers across the United States. Participants were aged 50 to 85 with early symptomatic AD. They were stratified by APOE ε4 status and amyloid burden at baseline. Participants randomized to donanemab could discontinue treatment upon 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 donanemab 700 mg 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 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). Danunemab was also superior in reducing plasma P-tau217.
The safety profiles of both treatments were consistent with previous study data. Dr. Salloway said that despite greater clearance of amyloid in the donanemab group, there was no difference in the incidence of amyloid-related imaging abnormalities, either characterized by edema and effusion or by cerebral micro-hemorrhages. The TRAILBLAZER-ALZ 4 study is ongoing, with analyses at 12 and 18 months underway.
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