Deposition of the beta (β)-amyloid in the brain is considered as early events seen in Alzheimer disease (AD) which leads to neurofibrillary tangles composed of tau protein with other characteristic brain changes referred to as the amyloid cascade. Over the past decade, medical therapeutic advances have pushed to pursue treatment for AD and numerous amyloid-targeting therapy trials failed to show appreciable slowing of the clinical disease progression until the development of the monoclonal antibodies. They have shown some promising results by promoting amyloid plaque clearance. Donanemab is an immunoglobulin G1 monoclonal antibody directed against insoluble, modified, N-terminal truncated form of β-amyloid. Recent trials have shown donanemab had the ability to slow the overall tau accumulation as well as reduce functional and cogition decline noted on the integrated Alzheimer’s Disease Rating Scale by up to 32%. Furthermore, the phase 2 TRIALBLAZER-ALZ trial showed some promising results of donanemab against placebo. Therefore, the TRIALBLAZER-ALZ 2, a global phase 3 randomised, double-blinded controlled trial with 1,736 participants with early AD (mild cognitive impairment/mild dementia) with amyloid low/medium or high tau pathology was performed. The study concluded that donanemab significantly slows the clinical progression of AD at 76 weeks by 80% in patients with low/medium tau with 47% of patients had no change in disease progression, compared to 29% of participants receiving placebo. Therefore, the study advocated the use of monoclonal antibodies during the early stages of the disease.

References:

Sims JR, et al. JAMA. 2023 Jul 17:e2313239. 

Rashad A, et al. Healthcare (Basel). 2022 Dec 22;11(1):32.