Donanemab Slows Decline in Patients With Early Symptomatic Alzheimer Disease

In patients with amyloid-positive early symptomatic Alzheimer disease, treatment with donanemab significantly slowed cognitive and functional decline, according to data presented at the 2023 Alzheimer’s Association International Conference (AAIC).

Donanemab is an investigational antibody therapy that targets a modified form of deposited amyloid-β peptide called N3pG. The randomized, double-blind, placebo-controlled TRAILBLAZER-ALZ 2 study (ClinicalTrials.gov Identifier: NCT04437511) evaluated the efficacy and safety of donanemab in adults 60 to 85 years of age with early symptomatic Alzheimer disease. Study participants were stratified by tau level into either a low/medium or high tau group.

Previous findings showed that among patients in the low/medium tau group (n=1182), donanemab was found to significantly slow clinical decline by 35% compared with placebo, based on the change from baseline on the integrated Alzheimer Disease Rating Scale (iADRS; primary endpoint) over 18 months (P <.0001). Donanemab also slowed clinical decline by 36% vs placebo on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; key secondary endpoint) over 18 months (P <.0001). Among all study participants (n=1736), treatment with donanemab significantly slowed decline by 22% on iADRS and 29% on CDR-SB.

New data presented at AAIC showed that among patients with mild cognitive impairment (n=214), donanemab slowed decline by 60% on iADRS and 46% on CDR-SB. The benefits of donanemab were also observed in patients with mild dementia due to Alzheimer disease (n=534); the treatment slowed decline by 30% on iADRS and 38% on CDR-SB in this patient population. A post-hoc subgroup analysis also demonstrated that among patients with low/medium tau, a greater benefit was seen in patients under 75 years of age treated with donanemab vs those aged 75 years and older.

Additionally, 47% of donanemab-treated patients with low/medium tau showed no decline on CDR-SB at 1-year vs 29% of patients who received placebo. In this population, treatment with donanemab was associated with a 39% lower risk of progressing to the next stage of disease over the 18-month trial.

Using amyloid positron emission tomography brain scan, findings showed significant reductions in brain amyloid plaque levels among patients in the donanemab arm as early as 6 months after initiating treatment. At 12 months, approximately half of all participants achieved predefined criteria of amyloid plaque clearance and were able to stop treatment. At 18 months, 7 of every 10 participants reached this threshold.

As for safety, amyloid-related imaging abnormalities of edema or effusion occurred in 24% and 2.1% of participants in the donanemab and placebo groups, respectively. Infusion-related reactions were reported in 8.7% of donanemab-treated patients and 0.5% of placebo patients.

Lilly has completed the submission of the application for donanemab with the Food and Drug Administration. A decision is expected by the end of the year.

This article originally appeared on MPR