Donanemab Superior to Aducanumab in Amyloid Clearance, Plaque Reductions

Donanemab use was associated with a higher rate of achieving amyloid clearance compared with aducanumab use in patients with early symptomatic Alzheimer disease (AD), according to study results presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held from April 22 to 27, in Boston, Massachusetts.

Study authors conducted a phase 3 clinical trial (TRAILBLAZER-ALZ 4; ClinicalTrials.gov Identifier: NCT05108922) to evaluate the superiority of donanemab in amyloid plaque clearance compared with aducanumab in patients with AD. Participants were randomly assigned 1:1 to receive either donanemab (n=71) or aducanumab (n=69) for a total of 6 months.

At baseline, 27 participants in the donanemab arm and 28 patients in the aducanumab arm were defined as having intermediate tau. Baseline brain amyloid levels for each arm:

• Donanemab arm: 98.29±27.83 centiloids (CL)
• Aducanumab arm: 102.40±35.49 CL
• Donanemab arm, intermediate tau: 104.97±25.68 CL
• Aducanumab arm, intermediate tau: 102.23±28.13 CL

Florbetapir F18 positron emission tomography (PET) scans taken at 6 months after initiation of therapy revealed that 37.9% and 1.6% of participants treated with donanemab vs aducanumab, respectively, achieved amyloid clearance (P <.001). Similar significance was seen in participants in the intermediate tau subpopulation (38.5% vs 3.8%, respectively; P = .008).

Significant percent changes in brain amyloid levels were seen in participants who received donanemab in both the original study population (-65.2%±3.9% vs -17.0%±4.0%; P <.001) and intermediate tau subpopulation (-63.9%±7.4% vs -25.4%±7.8%; P ≤.001), compared with those who received aducanumab.

Similar rates of adverse events were reported in the donanemab and aducanumab arms (62.0% vs 66.7%); 1 case of amyloid-related imaging abnormalities was reported in the aducanumab arm.

After 6 months of treatment with donanemab, more participants reached amyloid clearance and amyloid plaque reductions compared with aducanumab. “This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD [Alzheimer’s disease],” the study authors concluded.