In what could be a breakthrough for patients with Alzheimer’s disease, treatment with donanemab resulted in significant slowing down of disease progress in patients with early symptomatic AD, according to topline results of the TRAILBLAZER-ALZ 2 trial. Donanemab is an investigational drug, which acts against the amyloid plaques, which are the hallmark of AD. There is no cure for AD.

The randomized, double-blind, placebo-controlled TRAILBLAZER-ALZ 2 trial recruited people with early symptomatic AD to examine the safety and efficacy of donanemab. A total of 1182 persons with an intermediate level of tau and clinical symptoms of AD comprised the primary analysis population; 552 persons with baseline high tau levels were also selected for the study. Tau is a biomarker for AD.

Over 18 months of treatment with donanemab, decline in cognition and ADLs slowed down by 35% months on the integrated Alzheimers Disease Rating Scale (iADRS), the primary endpoint of the study. A 36% slowing of decline was noted on Clinical Dementia Rating-Sum of Boxes (CDR-S) with donanemab at one year, a secondary endpoint of the study which measures severity of disease.

No decline was observed on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in nearly half of patients (47%) at one year signifying no clinical progression compared to placebo recipients (29%).

Donanemab-treated patients had 40% less decline in the ability to carry out activities of daily living as assessed by Alzheimers Disease Cooperative Study – Instrumental Activities of Daily Living Inventory (ADCS-iADL). Patients in the donanemab group had a 39% lower risk of progressing to the next stage of disease compared to placebo (CDR-Global Score, hazard ratio [HR] 0.61). Additionally, brain amyloid plaque levels decreased significantly within 6 months of starting treatment. Based on the predefined levels of amyloid plaque clearance, 52% patients finished their treatment course by 1 year; 72% participants completed their treatment by 18 months. A separate combined analysis of participants with high tau and intermediate tau levels observed similar results; treatment with donanemab resulted in 29% slower decline on CDR-SB and 22% slower decline on iADRS.

Few side-effects were observed: amyloid-related imaging abnormalities (ARIA), cerebral edema (ARIA-E), cerebral microhemorrhages (ARIA-H) and infusion-related reactions. These could be a cause of concern.

Other data from the trial will be presented in July at the Alzheimers Association International Conference (AAIC) to be held in Amsterdam, Netherlands.

Reference

1. https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional, May 3, 2023. Accessed on May 4, 2023.