Top-line study results were released earlier this year. However, the researchers presented additional findings and perspectives at the Alzheimer's Association International Conference 2022.
The investigational anti-amyloid monoclonal antibody crenezumab (Genentech) is not superior to a placebo for change in cognition, brain imaging, or biomarker outcomes in individuals who are at genetically high risk for Alzheimer’s disease (AD), new research shows.
These findings from the Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) Colombia Trial, which included more than 250 participants, “are disappointing, actually heartbreaking; and we immediately think of the families,” Eric Reiman, MD, executive director, Banner Alzheimer’s Institute, Phoenix, Arizona, and co-leader of the trial, told Medscape Medical News.
However, though the group differences were not significant, the average annual change in clinical and biomarker measurements consistently favored the active treatment over placebo, and there are still important outstanding measures to come, Reiman noted. In addition, although the results were negative, the study provides a sort of template for future prevention trials, he said.
Crenezumab was designed to neutralize neurotoxic oligomers, a form of beta-amyloid, and to have a minimal inflammatory brain cell response. So it should reduce amyloid-related imaging abnormalities (ARIAs), a common side effect with other antibodies, said Reiman.
The API ADAD trial included 252 adults in Colombia who are aged 30-60 years.
About two-thirds of participants carried the PSEN1 E280A mutation, which virtually guarantees that carriers will develop mild cognitive impairment at an average age of 44 years, dementia at about 49 years, and death at about 59 years. At enrollment, all participants were cognitively unimpaired.
Colombia has the largest population in the world with this early onset autosomal dominant AD, investigators note.
“The analysis included 85 carriers taking crenezumab and 84 carriers taking a placebo. The study also included 83 noncarriers who received a placebo “to obviate the requirement for people to learn their genetic risk,” Reiman reported.
Parvathy Sukumaran 
