Treatment with solanezumab did not slow the progression of cognitive decline due to Alzheimer disease (AD) pathology in patients with amyloid plaque but no clinical symptoms of the disease, according to data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) study.
Solanezumab is an investigational humanized monoclonal antibody designed to increase clearance of soluble amyloid beta (Aβ) from the brain by binding to aggregated forms of Aβ. The phase 3 A4 study (ClinicalTrials.gov Identifier: NCT02008357) included more than 1100 patients 65 to 85 years of age with preclinical AD, defined as those with evidence of amyloid plaque build-up who are clinically unimpaired but at high risk for cognitive decline.
Patients were randomly assigned to receive either solanezumab or placebo intravenously every 4 weeks for approximately 4.5 years. The primary endpoint was the change from baseline in the Preclinical Alzheimer Cognitive Composite (PACC), an equally weighted composite that tests episodic memory, timed executive function, and global cognition.
Results showed solanezumab failed to slow cognitive decline based on PACC change; the mean change in PACC score was -1.69 compared with -1.4 for placebo (P =.26). Moreover, solanezumab did not meet secondary endpoints, with similar rates of progression observed in both groups on the Clinical Dementia Rating-Global Scale.
Patients in both treatment arms continued to accumulate amyloid over time, according to amyloid PET imaging. Findings also showed that higher baseline amyloid levels were associated with greater risk of progression to symptomatic disease (P <.001).
“Results of the A4 Study clearly showed that the primary and secondary endpoints were not met. Therefore, the A4 Study concludes our clinical development of solanezumab and indicates that targeting soluble amyloid beta through this mechanism is not effective in this population,” said John Sims, head of medical, global brand development – solanezumab, for Eli Lilly and Company. “While this study was negative, the unique data generated have increased our understanding of preclinical Alzheimer disease and will advance the next generation of AD prevention studies.”
Lilly will share full study results later this year.
Lilly provides update on A4 study of solanezumab for preclinical Alzheimer’s disease. News release. Eli Lilly and Company. Accessed March 9, 2023. https://www.prnewswire.com/news-releases/lilly-provides-update-on-a4-study-of-solanezumab-for-preclinical-alzheimers-disease-301766069.html.