Hereditary Alzheimer's: Long-Term Antibody Removal of Amyloid Shows Signs of Delayed Onset

Evidence has accumulated that monoclonal antibodies that clear amyloid slow progression after symptoms appear, but it was unknown whether they can delay the onset itself in people who do not yet have symptoms. The DIAN-TU team, led by Washington University School of Medicine in the United States, offered a clue to this question in Lancet Neurology.

A 3-year open-label extension after a double-blind phase 2/3 trial

The participants were carriers of dominantly inherited Alzheimer's disease, who inherit a causative mutation from a parent and almost certainly develop the disease. In an open-label extension study that followed a double-blind phase 2/3 platform trial, 73 people received gantenerumab by subcutaneous injection every two weeks at up to 1,500 mg. The study ended early when the drug company discontinued development, and 13 people completed the full three years.

The primary measure, the amyloid PET value (PiB-PET SUVR), fell by an average of 0.71 over three years. In an interim analysis, the hazard ratio for clinical worsening in asymptomatic carriers was 0.79 for all those with exposure to the drug and 0.53 for the 22 people treated the longest, but the confidence intervals all crossed 1. Amyloid-related imaging abnormalities (ARIA) appeared in 53%, with microhemorrhage in 47% and edema in 30%, and there were no major bleeds or deaths.

Limitations

Because the analysis relied on an open-label extension design and an external control group, the effect cannot be determined, and the researchers said it must be confirmed in a long-term randomized trial. The high frequency of adverse events must also be weighed.