Eli Lilly & Co’s Alzheimer’s disease drug fails to stop disease decline

pharmafile | March 9, 2023 | News story | Research and Development  

Eli Lilly & Co have today announced that its Alzheimer’s disease (AD) hopeful did not slow the progression of cognitive decline linked to the disease when initiated in individuals with amyloid plaque but no clinical symptoms of the disease.


Eli Lilly’s A4 study began in 2013 and was a first-of-its-kind, secondary prevention trial. It enrolled more than 1,100 individuals between 65-85 years old who had PET imaging-confirmed amyloid plaque accumulation in the brain but did not have clinical impairment. This is known as the preclinical stage of AD. Individuals were randomised to either receive solanezumab or placebo and were treated for four and a half years.


Solanezumab binds to soluble amyloid-beta protein ‒ stopping new plaques from building up ‒ and was not expected to significantly remove deposited amyloid plaques. However, the study revealed that solanezumab did not slow cognitive decline on the primary outcome measure, the Preclinical Alzheimer Cognitive Composite (PACC), and that 31% of patients starting at preclinical AD advanced on the Clinical Dementia Rating-Global Scale (CDR-GS). Amyloid continued to accumulate over time in both the placebo and solanezumab groups.


John Sims, head of medical, global brand development – solanezumab, for Eli Lilly & Co stated: “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. While this study was negative, the unique data generated have increased our understanding of preclinical AD and will advance the next generation of AD prevention studies. Raw data and analyses will be made widely available to researchers through the public-private partnership with the NIH-funded Alzheimer’s Clinical Trial Consortium. This data will serve the scientific community and enable Lilly and other drug developers to enhance our clinical trial designs for other potential medicines targeting AD.”


Eli Lilly will now focus on two other investigational antibodies currently in phase 3; donanemab and remternetug. These two drugs are different to solanezumab as they specifically target deposited amyloid plaque and have shown to lead to plaque clearance in treated individuals.


James Spargo

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