A phase 2 trial evaluating the efficacy and safety of crenezumab in adults with autosomal dominant Alzheimer disease (ADAD) did not meet its coprimary endpoints, according to Genentech.
ADAD is a rare, inherited form of Alzheimer disease caused by single gene mutations in the the APP, PSEN1 or PSEN2 genes. Crenezumab is an investigational monoclonal antibody designed to neutralize neurotoxic oligomers, a form of beta-amyloid, and minimize the inflammatory response in the brain.
The prospective, randomized, double-blind, placebo-controlled, parallel-group Alzheimer’s Prevention Initiative (API) ADAD Colombia Trial (ClinicalTrials.gov Identifier: NCT01998841) included 252 cognitively unimpaired adults who carry the PSEN1 E280A autosomal dominant mutation and have no clinical symptoms of Alzheimer disease. Patients were randomly assigned 1:1 to receive either crenezumab or placebo for at least 260 weeks.
Results showed that crenezumab did not demonstrate a statistically significant clinical benefit for the coprimary endpoints assessing the rate of change in cognitive abilities or episodic memory function, measured by the API ADAD composite cognitive score and the Free and Cued Selective Reminding Test Cueing Index, respectively.
“We’re disappointed that the treatment did not demonstrate a statistically significant clinical benefit,” said Eric M. Reiman, MD, Banner Alzheimer’s Institute executive director and one of the study leaders. “At the same time, we’re proud of the impact that this precedent-setting trial has had in shaping a new era in Alzheimer’s prevention research and we’re extremely grateful to our research participants and their families.”
Further analyses of data are ongoing. Initial trial data will be presented at the Alzheimer’s Association International Conference (AAIC) on August 2, 2022.
In 2019, Genentech discontinued phase 3 studies evaluating crenezumab in patients with early sporadic Alzheimer disease based on results indicating that the investigational treatment was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes score.
Genentech provides update on Alzheimer’s Prevention Initiative study evaluating crenezumab in autosomal dominant Alzheimer’s disease. News release. Genentech Inc. Accessed June 16, 2022. https://www.businesswire.com/news/home/20220616005106/en/Genentech-Provides-Update-on-Alzheimer%E2%80%99s-Prevention-Initiative-Study-Evaluating-Crenezumab-in-Autosomal-Dominant-Alzheimer%E2%80%99s-Disease