The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy. With an estimated 55 million people worldwide affected by dementia, the need for an effective treatment is undeniable. But efforts to develop a drug that can modify the course of Alzheimer’s disease, by using antibodies to clear amyloid-beta (Aβ) from the brain, have endured numerous setbacks over the past 20 years. Almost a decade ago, the first anti-Aβ antibodies tested in phase 3 trials, bapineuzumab and solanezumab, did not improve clinical outcomes in mild to moderate Alzheimer’s disease. Hopes were dashed again in 2019 when two phase 3 trials of aducanumab—one of the next generation of anti-Aβ antibodies that specifically target Aβ aggregates—were halted early for futility. Aducanumab’s resurrection and controversial approval in 2021 by the US Food and Drug Administration (FDA) under its accelerated approval programme, which allows early approval of drugs in areas of unmet need based on a positive change on a surrogate endpoint—in this case, amyloid reduction in the brain—sparked furore among the research community.

Read PDF: Leca Ph3 Lancet Editorial 3DEC2022