TRAILBLAZER-ALZ 4: Topline study results directly comparing donanemab to aducanumab on amyloid lowering in early, symptomatic Alzheimer’s disease
Stephen Salloway1, Elly Lee2, Michelle Papka3, Andrew Pain4, Ena Oru4, Margaret Ferguson4, Hong Wang4, Michael Case4, Ming Lu4, Emily Collins4, Dawn Brooks4, John Sims4
1Brown Medical School, 2Irvine Clinical Research, 3The Cognitive and Research Center of New Jersey LLC, 4Eli Lilly and Company
Objective:
To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer’s disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study.
Background:
The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.
Design/Methods:
Participants (n=148) were randomized 1:1 to receive donanemab (700mg IV Q4W [first 3 doses], then 1400mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1mg/kg IV Q4W [first 2 doses], 3mg/kg IV Q4W [next 2 doses], 6mg/kg IV Q4W [next 2 doses] and 10mg/kg IV Q4W [subsequent doses]).
Results:
Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N=71], aducanumab [N=69]). Twenty seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.
Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p<0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p=0.008).
Percent change in brain amyloid levels were -65.2%±3.9% (baseline: 98.29±27.83 CL) and -17.0%±4.0% (baseline: 102.40±35.49 CL) in donanemab and aducanumab arms, respectively (p<0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were -63.9%±7.4% (baseline: 104.97±25.68 CL) and -25.4%±7.8% (baseline: 102.23±28.13 CL) in donanemab and aducanumab arms, respectively (p≤0.001).
62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.
Conclusions:
This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.