Abstract

A REVIEW: EMERGING ROLE OF DONANEMAB IN THE MANAGEMENT OF ALZHEIMER’S DISEASE

Payal S. Bharad*, Dr. K. R. Biyani, Dr. R. H. Kale, Dr. R. A. Ingle, Dr. P. N. Folane

ABSTRACT

Alzheimer's disease (AD) remains a major challenge for modern medicine, affecting millions of people worldwide and placing a heavy burden on patients, their families and healthcare systems. Traditional symptomatic treatments, such as cholinesterase inhibitors and memantine, offer only limited relief. However, new disease-modifying therapies targeting amyloid beta (Aβ) plaques are beginning to change the picture. Donanemab, sold as Kisunla™, is a humanized monoclonal antibody designed to bind to and eliminate deposits of pyroglutamate-modified Aβ in the brain. Approved by the FDA in July 2024 for early symptomatic AD (mild cognitive impairment and mild stages of dementia), donanemab offers a way to slow disease progression.[11,17,18]This review synthesizes preclinical and clinical data, focusing on its mechanism of action, key trials such as theTRAILBLAZER-ALZ series, efficacy in reducing cognitive decline, and safety profile. In the pivotal phase 3 TRAILBLAZER-ALZ 2 trial, donanemab demonstrated a slowing of clinical progression by 22 to 35% over 76 weeks, with sustained benefits seen in long-term extensions of up to three years.[19,26] Amyloid plaque clearance was rapid, with more than 75% of patients reaching nadir levels by 76 weeks, allowing treatment discontinuation in many. cases.[12,23] However, safety concerns arose, particularly those related to amyloid. imaging abnormalities (ARIA), highlight the need for careful patient selection and follow-up, especially in ApoE ε4 homozygotes.[2,11] Comparison with other anti-Aβ treatments, such as lecanumab and aducanumab, highlights the unique plaque-specific targeting of donanemab, which potentially provides benefits in clearance efficiency but also confers similar risks.[8] Pharmacoeconomic analysis reveals high costs (approximately $32,000 per year in the US), raising questions about access and cost-effectiveness.[11] Future directions in the treatment of AD Including combination therapy and real-world studies to optimize its function.

Keywords: Alzheimer's disease, donanemab, beta-amyloid, monoclonal antibody, clinical trials, ARIA, disease-modifying therapy.