New beta-amyloid antibody drug treatments
Alzheimer’s research has seen significant progress in recent years with the development of monoclonal antibody treatments which target the protein amyloid. Amyloid clumps or plaque development in the brain have been correlated with Alzheimer’s disease progression. Beta-amyloid protein plaques are believed to disrupt cell-to-cell communication in the brain, causing inflammation resulting in brain cell death. Research in the development of anti-amyloid beta antibody drugs has received significant attention over the last few years.

The following discussion provides some context on both early advances and recent significant progress in the field of Alzheimer’s drug research. This research has led to the development of therapeutics such as gantenerumab (Roche and Genentech)², but many of these treatments have not progressed to the clinic as they failed to demonstrate a delay in cognitive decline in patients.

While early beta-amyloid antibody drugs haven’t shown as much progress as initially hoped, a recent antibody-based drug targeting the amyloid beta A4 protein is showing promise has recently received accelerated approval by the FDA.

Early Therapeutic Advances in Alzheimer’s Disease: Aducanumab (Aduhelm)
Beta-amyloid antibody drugs such as aducanumab (Aduhelm) gantenerumab and BAN2401 bind to soluble and insoluble amyloid beta aggregates. Aducanumab (Biogen’s Aduhelm) is a recombinant human antibody derived from a human blood lymphocyte which received “accelerated approval” from the FDA. It initially showed some promise, but its effectiveness in suppressing cognitive decline in Alzheimer’s needs further evaluation. It has also been found that there needs to be additional assessment of some identified adverse effects, such as brain swelling (ARIA-E edema/effusion) and bleeding (ARIA-H, cerebral microhemorrhages).

Recent Significant Progress in Alzheimer’s Drug Research: Lecanemab
Many of the initially developed beta-amyloid antibody treatments were halted due to significant side effects (including toxicity, brain swelling and bleeds) or limited effectiveness. But a newly approved drug, Lecanemab, shows promise.

Lecanemab’s development is significant because it is the first time that an amyloid antibody has been shown clinically to slow significant cognitive decline progression in Alzheimer’s patients. It has been reported to slow the rate of cognitive decline by 27% in controlled clinical studies. In early January 2023, Lecanemab was granted accelerated approval by the FDA for early-stage Alzheimer’s disease, though some drug-associated safety concerns remain.

The drug, developed by Biogen and Eisai, is an antibody which targets the amyloid beta A4 protein. It binds to amyloid beta protofibrils and is an anti-amyloid beta protofibril humanized monoclonal antibody.

Progress in Alzheimer’s drug discovery and development has historically trailed other disease states. But chemical communication software such as ChemDraw can help scientists accelerate research and bring drugs to market which improve health outcomes.