New research suggests a long-sought amyloid-lowering drug for Alzheimer's disease (AD) may soon be on the horizon. In a phase 1 clinical trial, a compound that blocks the enzyme BACE1, a major AD target, safely reduced toxic β-amyloid in 32 study participants with AD. Unlike other BACE1 inhibitors that cause severe side effects, the new drug proved safe, making it the first oral BACE1 inhibitor to advance to phase 3 trials, which are currently underway. β-amyloid (Aβ) is a sticky peptide that clumps into plaques, which damage the brain of individuals with AD. Blocking BACE1, which plays a key role in the production of Aβ, has emerged as a promising approach to rid the brain of amyloid buildup. However, the search for a brain-penetrant BACE1 inhibitor remains a challenge because of severe toxicity, which can lead to liver damage and further neurodegeneration. Matthew Kennedy and colleagues developed verubecestat, a potent and well-tolerated BACE1 inhibitor. A single dose of the drug markedly reduced levels of Aβ in the blood and cerebrospinal fluid of rats and monkeys. The animals showed no signs of toxicity even after extended treatment. In a phase 1 trial of healthy adults and patients with mild to moderate AD, single and multiple doses of verubecestat lowered Aβ levels without serious side effects. The promising results have helped launched phase 3 trials of the drug investigating its long-term outcomes in AD patients.