One of the leading theories for the cause of Alzheimer’s disease (AD) is the collection of abnormal amyloid plaques, a collection of misfolded amyloid A4 beta proteins (ABPP) that form in the spaces between nerve cells in the brain. This has led to a significant focus on producing drugs that inhibit ABPP, with leading data and analytics company GlobalData identifying that this mechanism of action (MoA) accounts for nearly one tenth of all drugs within the current AD pipeline. However, research by the University of Cincinnati has suggested that amyloid plaques may not be as responsible for AD as previously thought.

According to research by GlobalData’s Pharma Intelligence Center, there were 90 drugs in the AD pipeline targeting the ABPP MoA. To put this in perspective, there were 38% more drugs addressing the ABPP MoA than those targeting the next leading MoA, microtubule-associated protein tau (MAPT) inhibitors.

Quentin Horgan, Associate Director at GlobalData, comments: “Despite the pharma industries’ focus on ABPP, there have been very few successful drugs utilizing this MoA. Most infamously, Biogen’s supposed AD blockbuster aducanumab was an ABPP inhibitor that was approved by the FDA despite concerns around its efficacy (or lack thereof). The University of Cincinnati suggests that Alzheimer’s may actually be caused by a decline in the amount of amyloid beta available, suggesting that ABPP inhibitors may not be the best target.

“Despite the research, the future of AD appears to remain dominated by ABPP inhibitors, with three ABPP inhibitors hotly anticipated: Roche’s gantenerumab, Eisai’s lecanemab, and Eli Lilly’s donanemab. Furthermore, lecanemab had positive Phase III trial results in September.”